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Review

G-quadruplexes in cancer-related gene promoters: from identification to therapeutic targeting

, , ORCID Icon, , , , ORCID Icon, & ORCID Icon show all
Pages 745-773 | Received 26 Jun 2023, Accepted 11 Oct 2023, Published online: 25 Oct 2023

References

  • World Health Organization. Cancer. cited 2023 Jun 24. Available from: https://www.who.int/news-room/fact-sheets/detail/cancer
  • Palchaudhuri R, Hergenrother PJ. DNA as a target for anticancer compounds: methods to determine the mode of binding and the mechanism of action. Curr Opin Biotechnol. 2007;18(6):497–503. doi: 10.1016/j.copbio.2007.09.006
  • Hurley LH. DNA and its associated processes as targets for cancer therapy. Nat Rev Cancer. 2002;2(3):188–200. doi: 10.1038/nrc749
  • Cree IA, Charlton P. Molecular chess? Hallmarks of anti-cancer drug resistance. BMC Cancer. 2017;17(1):10. doi: 10.1186/s12885-016-2999-1
  • Choi J, Majima T. Conformational changes of non-B DNA. Chem Soc Rev. 2011;40(12):5893. doi: 10.1039/c1cs15153c
  • Spiegel J, Adhikari S, Balasubramanian S. The structure and function of DNA G-Quadruplexes. Trends Chem. 2020;2(2):123–136. doi: 10.1016/j.trechm.2019.07.002
  • Gellert M, Lipsett MN, Davies DR. Helix formation by guanylic acid. Proc Natl Acad Sci U S A. 1962;48(12):2013–2018. doi: 10.1073/pnas.48.12.2013
  • Zhou J, Bourdoncle A, Rosu F, et al. Tri-G-quadruplex: controlled assembly of a G-quadruplex structure from three G-rich strands. Angew Chem Int Ed Engl. 2012;51(44):11002–11005. doi: 10.1002/anie.201205390
  • Kolesnikova S, Curtis EA. Structure and function of multimeric G-quadruplexes. Molecules. 2019;24(17):1–20. doi: 10.3390/molecules24173074
  • Burge S, Parkinson GN, Hazel P, et al. Quadruplex DNA: sequence, topology and structure. Nucleic Acids Res. 2006;34(19):5402–5415. doi: 10.1093/nar/gkl655
  • Marsico G, Chambers VS, Sahakyan AB, et al. Whole genome experimental maps of DNA G-quadruplexes in multiple species. Nucleic Acids Res. 2019;47(8):3862–3874. doi: 10.1093/nar/gkz179
  • Hazel P, Huppert J, Balasubramanian S, et al. Loop-length-dependent folding of G-quadruplexes. J Am Chem Soc. 2004;126:16405–16415. doi: 10.1021/ja045154j
  • Hänsel-Hertsch R, Di Antonio M, Balasubramanian S. DNA G-quadruplexes in the human genome: detection, functions and therapeutic potential. Nat Rev Mol Cell Biol. 2017;18(5):279–284. doi: 10.1038/nrm.2017.3
  • Gomez DE, Armando RG, Farina HG, et al. Telomere structure and telomerase in health and disease. Int J Oncol. 2012;41(5):1561–1569. doi: 10.3892/ijo.2012.1611
  • Biffi G, Tannahill D, McCafferty J, et al. Quantitative visualization of DNA G-quadruplex structures in human cells. Nat Chem. 2013;5(3):182–186. doi: 10.1038/nchem.1548
  • Kouzine F, Wojtowicz D, Yamane A, et al. In vivo chemical probing for G-quadruplex formation. Methods Mol Biol. 2019;2035:369–382. doi: 10.1007/978-1-4939-9666-7_23
  • Huppert JL, Bugaut A, Kumari S, et al. G-quadruplexes: the beginning and end of UTRs. Nucleic Acids Res. 2008;36(19):6260–6268. doi: 10.1093/nar/gkn511
  • Georgakopoulos-Soares I, Parada GE, Wong HY, et al. Alternative splicing modulation by G-quadruplexes. Nat Commun. 2022;13(1):2404. doi: 10.1038/s41467-022-30071-7
  • Xu Y, Suzuki Y, Ito K, et al. Telomeric repeat-containing RNA structure in living cells. Proc Natl Acad Sci. 2010;107(33):14579–14584. doi: 10.1073/pnas.1001177107
  • Kharel P, Becker G, Tsvetkov V, et al. Properties and biological impact of RNA G-quadruplexes: from order to turmoil and back. Nucleic Acids Res. 2020;48(22):12534–12555. doi: 10.1093/nar/gkaa1126
  • Di Porzio A, Galli U, Amato J, et al. Synthesis and characterization of Bis-Triazolyl-Pyridine derivatives as noncanonical DNA-Interacting compounds. Int J Mol Sci. 2021;22(21):11959. doi: 10.3390/ijms222111959
  • Kosiol N, Juranek S, Brossart P, et al. G-quadruplexes: a promising target for cancer therapy. Mol Cancer. 2021;20(1):40. doi: 10.1186/s12943-021-01328-4
  • Wang Y-H, Yang Q-F, Lin X, et al. G4LDB 2.2: a database for discovering and studying G-quadruplex and i-motif ligands. Nucleic Acids Res. 2022;50(D1):D150–60. doi: 10.1093/nar/gkab952
  • Carvalho J, Mergny J-L, Salgado GF, et al. G-quadruplex, friend or foe: the role of the G-quartet in anticancer strategies. Trends Mol Med. 2020;26(9):848–861. doi: 10.1016/j.molmed.2020.05.002
  • Mishra SK, Tawani A, Mishra A, et al. G4IPDB: a database for G-quadruplex structure forming nucleic acid interacting proteins. Sci Rep. 2016;6(1):38144. doi: 10.1038/srep38144
  • Hänsel-Hertsch R, Beraldi D, Lensing SV, et al. G-quadruplex structures mark human regulatory chromatin. Nat Genet. 2016;48(10):1267–1272. doi: 10.1038/ng.3662
  • Hänsel-Hertsch R, Spiegel J, Marsico G, et al. Genome-wide mapping of endogenous G-quadruplex DNA structures by chromatin immunoprecipitation and high-throughput sequencing. Nat Protoc. 2018;13(3):551–564. doi: 10.1038/nprot.2017.150
  • Liu M, Yu K, Lian W, et al. G-quadruplex structures as a “Switch” regulate ATF4 expression in ferroptotic HepG2 cells. ACS Chem Biol. 2023;18(2):273–284. doi: 10.1021/acschembio.2c00615
  • Brown R, Gaerig V, Simmons T, et al. Helping Eve overcome ADAM: G-Quadruplexes in the ADAM-15 promoter as New molecular targets for breast cancer therapeutics. Molecules. 2013;18(12):15019–15034. doi: 10.3390/molecules181215019
  • Zhang L, Yan T, Wang W, et al. AKT1 is positively regulated by G-quadruplexes in its promoter and 3´-UTR. Biochem Biophys Res Commun. 2021;561:93–100. doi: 10.1016/j.bbrc.2021.05.029
  • Mitchell T, Ramos-Montoya A, Di Antonio M, et al. Downregulation of androgen receptor transcription by promoter G-Quadruplex stabilization as a potential alternative treatment for castrate-resistant prostate cancer. Biochemistry. 2013;52(8):1429–1436. doi: 10.1021/bi301349c
  • Schlag K, Steinhilber D, Karas M, et al. Analysis of proximal ALOX5 promoter binding proteins by quantitative proteomics. FEBS J. 2020;287(20):4481–4499. doi: 10.1111/febs.15259
  • Yan T, Zhao B, Wu Q, et al. Characterization of G-quadruplex formation in the ARID1A promoter. Int j biol macromol. 2020;147:750–761. doi: 10.1016/j.ijbiomac.2020.01.210
  • Greco ML, Folini M, Sissi C. Double stranded promoter region of BRAF undergoes to structural rearrangement in nearly physiological conditions. FEBS Lett. 2015;589(16):2117–2123. doi: 10.1016/j.febslet.2015.06.025
  • Wang K-B, Liu Y, Li Y, et al. Oxidative damage induces a vacancy G-Quadruplex that binds guanine metabolites: solution structure of a cGMP Fill-in vacancy G-Quadruplex in the oxidized BLM gene promoter. J Am Chem Soc. 2022;144(14):6361–6372. doi: 10.1021/jacs.2c00435
  • Li Y, Zhang X, Gao Y, et al. G-quadruplexes in the BAP1 promoter positively regulate its expression. Exp Cell Res. 2018;369(1):147–157. doi: 10.1016/j.yexcr.2018.05.016
  • Moruno-Manchon JF, Koellhoffer EC, Gopakumar J, et al. The G-quadruplex DNA stabilizing drug pyridostatin promotes DNA damage and downregulates transcription of Brca1 in neurons. Aging. 2017;9(9):1957–1970. doi: 10.18632/aging.101282
  • Swafford K, Acharya B, Xu Y-Z, et al. Targeting a novel G-Quadruplex in the CARD11 oncogene promoter with Naptho(2,1-b)furan-1-ethanol,2-nitro- requires the Nitro group. Genes (Basel). 2022;13(7):1144. doi: 10.3390/genes13071144
  • Zizza P, Cingolani C, Artuso S, et al. Intragenic G-quadruplex structure formed in the human CD133 and its biological and translational relevance. Nucleic Acids Res. 2016;44(4):1579–1590. doi: 10.1093/nar/gkv1122
  • Huang M-C, Chu I-T, Wang Z-F, et al. A G-Quadruplex structure in the promoter region of CLIC4 functions as a regulatory element for gene expression. Int J Mol Sci. 2018;19(9):2678. doi: 10.3390/ijms19092678
  • Yaşar P, Kars G, Yavuz K, et al. A CpG island promoter drives the CXXC5 gene expression. Sci Rep. 2021;11(1):15655. doi: 10.1038/s41598-021-95165-6
  • Zafar MK, Hazeslip L, Chauhan MZ, et al. The expression of human DNA helicase B is affected by G-quadruplexes in the promoter. Biochemistry. 2020;59(26):2401–2409. doi: 10.1021/acs.biochem.0c00218
  • Greco ML, Kotar A, Rigo R, et al. Coexistence of two main folded G-quadruplexes within a single G-rich domain in the EGFR promoter. Nucleic Acids Res. 2017;45(17):10132–10142. doi: 10.1093/nar/gkx678
  • Zhang L, Tan W, Zhou J, et al. Investigation of G-quadruplex formation in the FGFR2 promoter region and its transcriptional regulation by liensinine. Biochim Biophys Acta - Gen Subj. 2017;1861(4):884–891. doi: 10.1016/j.bbagen.2017.01.028
  • Wei P-C, Wang Z-F, Lo W-T, et al. A cis-element with mixed G-quadruplex structure of NPGPx promoter is essential for nucleolin-mediated transactivation on non-targeting siRNA stress. Nucleic Acids Res. 2013;41(3):1533–1543. doi: 10.1093/nar/gks1232
  • Fukuhara M, Ma Y, Nagasawa K, et al. A G-quadruplex structure at the 5´ end of the H19 coding region regulates H19 transcription. Sci Rep. 2017;7(1):45815. doi: 10.1038/srep45815
  • Ohnmacht SA, Micco M, Petrucci V, et al. Sequences in the HSP90 promoter form G-quadruplex structures with selectivity for disubstituted phenyl bis-oxazole derivatives. Bioorg Med Chem Lett. 2012;22(18):5930–5935. doi: 10.1016/j.bmcl.2012.07.065
  • Qiu J, Liu J, Chen S, et al. Role of hairpin-quadruplex DNA secondary structural conversion in the promoter of hnRNP K in gene transcriptional regulation. Org Lett. 2015;17(18):4584–4587. doi: 10.1021/acs.orglett.5b02310
  • Zhang X, Zhao B, Yan T, et al. G-quadruplex structures at the promoter of HOXC10 regulate its expression. Biochim Biophys Acta - Genet Regul Mech. 2018;1861(11):1018–1028. doi: 10.1016/j.bbagrm.2018.09.004
  • Cui X, Chen H, Zhang Q, et al. Exploration of the structure and recognition of a G-quadruplex in the her2 proto-oncogene promoter and its transcriptional regulation. Sci Rep. 2019;9(1):3966. doi: 10.1038/s41598-019-39941-5
  • Nishikawa T, Kuwano Y, Nakata M, et al. Multiple G-quadruplexes in the LMNA promoter regulate LMNA variant 6 transcription and promote colon cancer cell growth. Biochim Biophys Acta - Genet Regul Mech. 2021;1864(10):194746. doi: 10.1016/j.bbagrm.2021.194746
  • Robert C, Marquevielle J, Salgado GF. The promoter region of the proto-oncogene MST1R contains the main features of G-quadruplexes formation. Int J Mol Sci. 2022;23(21):12905. doi: 10.3390/ijms232112905
  • Lago S, Nadai M, Ruggiero E, et al. The MDM2 inducible promoter folds into four-tetrad antiparallel G-quadruplexes targetable to fight malignant liposarcoma. Nucleic Acids Res. 2021;49(2):847–863. doi: 10.1093/nar/gkaa1273
  • Stevens AJ, Stuffrein-Roberts S, Cree SL, et al. Correction: G-Quadruplex structures and CpG methylation cause drop-out of the maternal allele in polymerase chain reaction amplification of the imprinted MEST gene promoter. PLoS One. 2015;10:e0122940.
  • Yan J, Zhao X, Liu B, et al. An intramolecular G-quadruplex structure formed in the human MET promoter region and its biological relevance. Mol Carcinog. 2016;55(5):897–909. doi: 10.1002/mc.22330
  • Yan J, Zhao D, Dong L, et al. A novel G-quadruplex motif in the human MET promoter region. Biosci Rep. 2017;37(6):BSR20171128. doi: 10.1042/BSR20171128
  • Joshi S, Singh A, Kukreti S. Porphyrin induced structural destabilization of a parallel DNA G‐quadruplex in human MRP1 gene promoter. J Mol Recognit. 2022;35(3):1–14. doi: 10.1002/jmr.2950
  • Yang M, Carter S, Parmar S, et al. Targeting a noncanonical, hairpin-containing G-quadruplex structure from the MYCN gene. Nucleic Acids Res. 2021;49(14):7856–7869. doi: 10.1093/nar/gkab594
  • Fleming AM, Zhu J, Ding Y, et al. Human DNA repair genes possess potential G-Quadruplex sequences in their promoters and 5´-untranslated regions. Biochemistry. 2018;57(6):991–1002. doi: 10.1021/acs.biochem.7b01172
  • Renčiuk D, Ryneš J, Kejnovská I, et al. G-quadruplex formation in the Oct4 promoter positively regulates Oct4 expression. Biochim Biophys Acta - Genet Regul Mech. 2017;1860(2):175–183. doi: 10.1016/j.bbagrm.2016.11.002
  • Li F, Zhou J, Xu M, et al. Investigation on the formation, conversion and bioactivity of a G-quadruplex structure in the PALB2 gene. Int j biol macromol. 2016;83:242–248. doi: 10.1016/j.ijbiomac.2015.11.069
  • Zhu J, Fleming AM, Burrows CJ. The RAD17 promoter sequence contains a potential tail-dependent G-Quadruplex that downregulates gene expression upon oxidative modification. ACS Chem Biol. 2018;13(9):2577–2584. doi: 10.1021/acschembio.8b00522
  • Lin S, Gu H, Xu M, et al. The formation and stabilization of a novel G-Quadruplex in the 5´-Flanking region of the relaxin gene. PLoS One. 2012;7(2):e31201. doi: 10.1371/journal.pone.0031201
  • Xu Y, Sugiyama H. Structural and functional characterizations of the G-quartet and i-motif elements in retinoblastoma susceptibility genes (Rb). Nucleic Acids Symp Ser. 2005;49(1):177–178. doi: 10.1093/nass/49.1.177
  • Ahmed A A. The Potent G-Quadruplex-Binding Compound QN-302 Downregulates S100P Gene Expression in Cells and in an In Vivo Model of Pancreatic Cancer. Molecules. 2023;28(6):2452. doi: 10.3390/molecules28062452.
  • Lin S, Long H, Zhou J, et al. Study of G-quadruplexes in the STAT3 gene using electrospray ionization mass spectrometry. Rapid Commun Mass Spectrom. 2016;30(S1):173–178. doi: 10.1002/rcm.7640
  • Lin S, Li S, Chen Z, et al. Formation, recognition and bioactivities of a novel G-quadruplex in the STAT3 gene. Bioorg Med Chem Lett. 2011;21(19):5987–5991. doi: 10.1016/j.bmcl.2011.07.121
  • Lin S, Xu M, Yuan G. Study of STAT3 G-quadruplex folding patterns by CD spectroscopy and molecular modeling. Chinese Chem Lett. 2012;23(3):329–331. doi: 10.1016/j.cclet.2011.11.002
  • Wang Y, Yan T, Li J, et al. The SNAIL1 promoter contains G-quadruplex structures regulating its gene expression and DNA replication. Exp Cell Res. 2020;394(2):112158. doi: 10.1016/j.yexcr.2020.112158
  • Rezzoug F, Thomas SD, Rouchka EC, et al. Discovery of a family of genomic sequences which interact specifically with the c-MYC promoter to regulate c-MYC expression. PLoS One. 2016;11(8):e0161588. doi: 10.1371/journal.pone.0161588
  • Benabou S, Mazzini S, Aviñó A, et al. A pH-dependent bolt involving cytosine bases located in the lateral loops of antiparallel G-quadruplex structures within the SMARCA4 gene promotor. Sci Rep. 2019;9(1):15807. doi: 10.1038/s41598-019-52311-5
  • Cozzaglio M, Ceschi S, Groaz E, et al. G-quadruplexes formation within the promoter of TEAD4 oncogene and their interaction with Vimentin. Front Chem. 2022;10: doi: 10.3389/fchem.2022.1008075
  • Nishikawa T, Kuwano Y, Takahara Y, et al. HnRNPA1 interacts with G-quadruplex in the TRA2B promoter and stimulates its transcription in human colon cancer cells. Sci Rep. 2019;9(1):10276. doi: 10.1038/s41598-019-46659-x
  • Agarwala P, Pandey S, Mapa K, et al. The G-quadruplex augments translation in the 5´ untranslated region of transforming growth factor β2. Biochemistry. 2013;52(9):1528–1538. doi: 10.1021/bi301365g
  • Salvati E, Zizza P, Rizzo A, et al. Evidence for G-quadruplex in the promoter of vegfr-2 and its targeting to inhibit tumor angiogenesis. Nucleic Acids Res. 2014;42(5):2945–2957. doi: 10.1093/nar/gkt1289
  • Liu Y, Lan W, Wang C, et al. Correction: a putative G-quadruplex structure in the proximal promoter of VEGFR-2 has implications for drug design to inhibit tumor angiogenesis. J Biol Chem. 2019;294(27):10740. doi: 10.1074/jbc.AAC119.009662
  • Kuo M-J, Wang Z-F, Tseng T-Y, et al. Conformational transition of a hairpin structure to G-quadruplex within the WNT1 gene promoter. J Am Chem Soc. 2015;137(1):210–218. doi: 10.1021/ja5089327
  • Wang Z-F, Li M-H, Chu I-T, et al. Cytosine epigenetic modification modulates the formation of an unprecedented G4 structure in the WNT1 promoter. Nucleic Acids Res. 2020;48(3):1120–1130. doi: 10.1093/nar/gkz1207
  • Zhang R, Lin Y, Zhang C-T. Greglist: a database listing potential G-quadruplex regulated genes. Nucleic Acids Res. 2008;36(suppl_1):D372–6. doi: 10.1093/nar/gkm787
  • Roy A, Basu D, Bose D, et al. Identification and characterization of a flexile G-quadruplex in the distal promoter region of stemness gene REX1. Int j biol macromol. 2023;231:123263. doi: 10.1016/j.ijbiomac.2023.123263
  • Dutta A, Maji N, Sengupta P, et al. Promoter G-quadruplex favours epigenetic reprogramming-induced atypical expression of ZEB1 in cancer cells. Biochim Biophys Acta - Gen Subj. 2021;1865(8):129899. doi: 10.1016/j.bbagen.2021.129899
  • Malumbres M, Barbacid M. RAS oncogenes: the first 30 years. Nat Rev Cancer. 2003;3(6):459–465. doi: 10.1038/nrc1097
  • Dhillon AS, Hagan S, Rath O, et al. MAP kinase signalling pathways in cancer. Oncogene. 2007;26(22):3279–3290. doi: 10.1038/sj.onc.1210421
  • Eser S, Schnieke A, Schneider G, et al. Oncogenic KRAS signalling in pancreatic cancer. Br J Cancer. 2014;111(5):817–822. doi: 10.1038/bjc.2014.215
  • Moore AR, Rosenberg SC, McCormick F, et al. Author Correction: RAS-targeted therapies: is the undruggable drugged? Nat Rev Drug Discov. 2020;19(12):902–902. doi: 10.1038/s41573-020-0089-1
  • Kamisawa T, Wood LD, Itoi T, et al. Pancreatic cancer. Lancet. 2016;388(10039):73–85. doi: 10.1016/S0140-6736(16)00141-0
  • Zhu G, Pei L, Xia H, et al. Role of oncogenic KRAS in the prognosis, diagnosis and treatment of colorectal cancer. Mol Cancer. 2021;20(1):143. doi: 10.1186/s12943-021-01441-4
  • Skoulidis F, Heymach JV. Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy. Nat Rev Cancer. 2019;19(9):495–509. doi: 10.1038/s41568-019-0179-8
  • Cogoi S, Quadrifoglio F, Xodo LE. G-rich oligonucleotide inhibits the binding of a nuclear protein to the Ki- ras promoter and strongly reduces cell growth in human carcinoma pancreatic cells. Biochemistry. 2004;43(9):2512–2523. doi: 10.1021/bi035754f
  • Cogoi S, Xodo LE. G-quadruplex formation within the promoter of the KRAS proto-oncogene and its effect on transcription. Nucleic Acids Res. 2006;34(9):2536–2549. doi: 10.1093/nar/gkl286
  • Cogoi S, Paramasivam M, Spolaore B, et al. Structural polymorphism within a regulatory element of the human KRAS promoter: formation of G4-DNA recognized by nuclear proteins. Nucleic Acids Res. 2008;36(11):3765–3780. doi: 10.1093/nar/gkn120
  • Morgan RK, Batra H, Gaerig VC, et al. Identification and characterization of a new G-quadruplex forming region within the KRAS promoter as a transcriptional regulator. Biochim Biophys Acta - Genet Regul Mech. 2016;1859(2):235–245. doi: 10.1016/j.bbagrm.2015.11.004
  • Marquevielle J, Robert C, Lagrabette O, et al. Structure of two G-quadruplexes in equilibrium in the KRAS promoter. Nucleic Acids Res. 2020;48(16):9336–9345. doi: 10.1093/nar/gkaa387
  • D’Aria F, Pagano B, Petraccone L, et al. KRAS promoter G-quadruplexes from sequences of different length: a physicochemical study. Int J Mol Sci. 2021;22(1):448. doi: 10.3390/ijms22010448
  • Paramasivam M, Cogoi S, Xodo LE. Primer extension reactions as a tool to uncover folding motifs within complex G-rich sequences: analysis of the human KRAS NHE. Chem Commun. 2011;47(17):4965. doi: 10.1039/c1cc10269a
  • Kerkour A, Marquevielle J, Ivashchenko S, et al. High-resolution three-dimensional NMR structure of the KRAS proto-oncogene promoter reveals key features of a G-quadruplex involved in transcriptional regulation. J Biol Chem. 2017;292(19):8082–8091. doi: 10.1074/jbc.M117.781906
  • Ou A, Schmidberger JW, Wilson KA, et al. High resolution crystal structure of a KRAS promoter G-quadruplex reveals a dimer with extensive poly-A π-stacking interactions for small-molecule recognition. Nucleic Acids Res. 2020;48(10):5766–5776. doi: 10.1093/nar/gkaa262
  • Pattanayak R, Barua A, Das A, et al. Porphyrins to restrict progression of pancreatic cancer by stabilizing KRAS G-quadruplex: In silico, in vitro and in vivo validation of anticancer strategy. Eur J Pharm Sci. 2018;125:39–53. doi: 10.1016/j.ejps.2018.09.011
  • Caterino M, D’Aria F, Kustov AV, et al. Selective binding of a bioactive porphyrin-based photosensitizer to the G-quadruplex from the KRAS oncogene promoter. Int j biol macromol. 2020;145:244–251. doi: 10.1016/j.ijbiomac.2019.12.152
  • Lavrado J, Borralho PM, Ohnmacht SA, et al. ChemMedChem abstract: synthesis, G-Quadruplex stabilization, docking studies, and effect on cancer cells of Indolo[3,2-b]quinolines with one, two, or three basic side chains. ChemInform. 2013;45(8):n/a–n/a. doi: 10.1002/chin.201408184
  • Brito H, Martins AC, Lavrado J, et al. Targeting KRAS oncogene in colon cancer cells with 7-carboxylate Indolo[3,2-b]quinoline tri-alkylamine derivatives. PLoS One. 2015;10(5):e0126891. doi: 10.1371/journal.pone.0126891
  • He Q, Liu X, Li L. CN113150054A. 2021.
  • Ou T-M, Peng W, Sun ZY, et al. CN108530453A. 2018.
  • Chand K, Jamroskovic J, Doimo M. WO2020263164A1. 2020.
  • Hu MH. CN110283132A. 2019.
  • Li Z, Liu Z. CN112300148A. 2021.
  • Huang Z, Li M, Tan J, et al. CN113387934A. 2021.
  • Teply F, Hajek M, Kuzmova E, et al. US 9932339.
  • Rice WG, Howell SH, Tsai CY. US 11149047. 2021.
  • Rodríguez Villar J, Mascareñas Cid JL, Rodríguez Couceiro J, et al. US 11471467.
  • Henary M, Wilson WD. US 11572475. 2023.
  • Schneekloth JJ, Simmons J, Felsenstein K, et al. US 20210261516. 2021.
  • Cushman MS, Yang D, Wu G, et al. US 20210382058. 2021.
  • Hurley L, De B, Chappeta VR, et al. US 20220098210. 2022.
  • Yuan G, Shaojing W, Jin L. CN108017652A. 2018.
  • Sintim HO, Zhou J, Wang C, et al. US 2019/0209548. 2019.
  • Ahmed Anno MA, Zhang K, Zhang M, et al. CN115385890A. 2022.
  • Hurley L, Gokhale V, Kang HJ, et al. US 20210371375. 2021.
  • She M, Lu YJ, Wu S, et al. CN113773302A. 2021.
  • Wang K-B, Liu Y, Li J, et al. Structural insight into the bulge-containing KRAS oncogene promoter G-quadruplex bound to berberine and coptisine. Nat Commun. 2022;13(1):6016. doi: 10.1038/s41467-022-33761-4
  • Amato J, Madanayake TW, Iaccarino N, et al. HMGB1 binds to the KRAS promoter G-quadruplex: a new player in oncogene transcriptional regulation? Chem Commun. 2018;54(68):9442–9445. doi: 10.1039/C8CC03614D
  • David AP, Pipier A, Pascutti F, et al. CNBP controls transcription by unfolding DNA G-quadruplex structures. Nucleic Acids Res. 2019;47(15):7901–7913. doi: 10.1093/nar/gkz527
  • Pramanik S, Chen Y, Song H, et al. The human AP-endonuclease 1 (APE1) is a DNA G-quadruplex structure binding protein and regulates KRAS expression in pancreatic ductal adenocarcinoma cells. Nucleic Acids Res. 2022;50(6):3394–3412. doi: 10.1093/nar/gkac172
  • Paramasivam M, Membrino A, Cogoi S, et al. Protein hnRNP A1 and its derivative Up1 unfold quadruplex DNA in the human KRAS promoter: implications for transcription. Nucleic Acids Res. 2009;37(9):2841–2853. doi: 10.1093/nar/gkp138
  • Cogoi S, Rapozzi V, Cauci S, et al. Critical role of hnRNP A1 in activating KRAS transcription in pancreatic cancer cells: a molecular mechanism involving G4 DNA. Biochim Biophys Acta - Gen Subj. 2017;1861(5):1389–1398. doi: 10.1016/j.bbagen.2016.11.031
  • Ferino A, Marquevielle J, Choudhary H, et al. hnRNPA1/UP1 unfolds KRAS G-quadruplexes and feeds a regulatory axis controlling gene expression. ACS Omega. 2021;6(49):34092–34106. doi: 10.1021/acsomega.1c05538
  • Cogoi S, Paramasivam M, Membrino A, et al. The KRAS promoter responds to myc-associated zinc finger and poly(ADP-ribose) polymerase 1 proteins, which recognize a critical quadruplex-forming GA-element. J Biol Chem. 2010;285(29):22003–22016. doi: 10.1074/jbc.M110.101923
  • Kaiser CE, Van Ert NA, Agrawal P, et al. Insight into the complexity of the i-motif and G-quadruplex DNA structures formed in the KRAS promoter and subsequent drug-induced gene repression. J Am Chem Soc. 2017;139(25):8522–8536. doi: 10.1021/jacs.7b02046
  • Schubbert S, Shannon K, Bollag G. Hyperactive ras in developmental disorders and cancer. Nat Rev Cancer. 2007;7(4):295–308. doi: 10.1038/nrc2109
  • Howell GM, Hodak SP, Yip L. RAS mutations in thyroid cancer. Oncology. 2013;18(8):926–932. doi: 10.1634/theoncologist.2013-0072
  • Cox AD, Fesik SW, Kimmelman AC, et al. Drugging the undruggable RAS: mission possible? Nat Rev Drug Discov. 2014;13(11):828–851. doi: 10.1038/nrd4389
  • Dinney CPN, McConkey DJ, Millikan RE, et al. Focus on bladder cancer. Cancer Cell. 2004;6(2):111–116. doi: 10.1016/j.ccr.2004.08.002
  • Vageli D, Kiaris H, Delakas D, et al. Transcriptional activation of H-ras, K-ras and N-ras proto-oncogenes in human bladder tumors. Cancer Lett. 1996;107(2):241–247. doi: 10.1016/0304-3835(96)04372-8
  • Mo L, Zheng X, Huang H-Y, et al. Hyperactivation of Ha-ras oncogene, but not Ink4a/Arf deficiency, triggers bladder tumorigenesis. J Clin Invest. 2007;117(2):314–325. doi: 10.1172/JCI30062
  • Mandalà M, Merelli B, Massi D. NRAS in melanoma: targeting the undruggable target. Crit Rev Oncol Hematol. 2014;92(2):107–122. doi: 10.1016/j.critrevonc.2014.05.005
  • Membrino A, Cogoi S, Pedersen EB, et al. G4-DNA formation in the HRAS promoter and rational design of decoy oligonucleotides for cancer therapy. PLoS One. 2011;6(9):e24421. doi: 10.1371/journal.pone.0024421
  • Cogoi S, Shchekotikhin AE, Xodo LE. HRAS is silenced by two neighboring G-quadruplexes and activated by MAZ, a zinc-finger transcription factor with DNA unfolding property. Nucleic Acids Res. 2014;42(13):8379–8388. doi: 10.1093/nar/gku574
  • Miglietta G, Cogoi S, Pedersen EB, et al. GC-elements controlling HRAS transcription form i-motif structures unfolded by heterogeneous ribonucleoprotein particle A1. Sci Rep. 2015;5(1):18097. doi: 10.1038/srep18097
  • Cogoi S, Shchekotikhin AE, Membrino A, et al. Guanidino anthrathiophenediones as G-Quadruplex binders: uptake, intracellular localization, and anti-harvey-ras gene activity in bladder cancer cells. J Med Chem. 2013;56(7):2764–2778. doi: 10.1021/jm3019063
  • Cogoi S, Zorzet S, Shchekotikhin AE, et al. Potent apoptotic response induced by chloroacetamidine anthrathiophenediones in bladder cancer cells. J Med Chem. 2015;58(14):5476–5485. doi: 10.1021/acs.jmedchem.5b00409
  • Cogoi S, Xodo LE. G4 DNA in ras genes and its potential in cancer therapy. Biochim Biophys Acta - Genet Regul Mech. 2016;1859(4):663–674. doi: 10.1016/j.bbagrm.2016.02.002
  • Kumari S, Bugaut A, Huppert JL, et al. An RNA G-quadruplex in the 5´ UTR of the NRAS proto-oncogene modulates translation. Nat Chem Biol. 2007;3(4):218–221. doi: 10.1038/nchembio864
  • Kumari S, Bugaut A, Balasubramanian S. Position and stability are determining factors for translation repression by an RNA G-quadruplex-forming sequence within the 5´ UTR of the NRAS proto-oncogene. Biochemistry. 2008;47(48):12664–12669. doi: 10.1021/bi8010797
  • Herdy B, Mayer C, Varshney D, et al. Analysis of NRAS RNA G-quadruplex binding proteins reveals DDX3X as a novel interactor of cellular G-quadruplex containing transcripts. Nucleic Acids Res. 2018;46(21):11592–11604. doi: 10.1093/nar/gky861
  • Bugaut A, Rodriguez R, Kumari S, et al. Small molecule-mediated inhibition of translation by targeting a native RNA G-quadruplex. Org Biomol Chem. 2010;8(12):2771. doi: 10.1039/c002418j
  • Katsuda Y, Sato S, Asano L, et al. A small molecule that represses translation of G-quadruplex-containing mRNA. J Am Chem Soc. 2016;138(29):9037–9040. doi: 10.1021/jacs.6b04506
  • Kawauchi K, Sugimoto W, Yasui T, et al. An anionic phthalocyanine decreases NRAS expression by breaking down its RNA G-quadruplex. Nat Commun. 2018;9(1):2271. doi: 10.1038/s41467-018-04771-y
  • Ou T-M, Lu Y-J, Zhang C, et al. Stabilization of G-Quadruplex DNA and down-regulation of oncogene c - myc by quindoline derivatives. J Med Chem. 2007;50(7):1465–1474. doi: 10.1021/jm0610088
  • Wang X-D, Ou T-M, Lu Y-J, et al. Turning off transcription of the bcl-2 gene by stabilizing the bcl-2 promoter quadruplex with quindoline derivatives. J Med Chem. 2010;53(11):4390–4398. doi: 10.1021/jm100445e
  • Liu H-Y, Chen A-C, Yin Q-K, et al. New disubstituted quindoline derivatives inhibiting Burkitt’s lymphoma cell proliferation by impeding c-MYC transcription. J Med Chem. 2017;60(13):5438–5454. doi: 10.1021/acs.jmedchem.7b00099
  • Peng W, Sun Z-Y, Zhang Q, et al. Design, synthesis, and evaluation of novel p -(methylthio)styryl substituted quindoline derivatives as neuroblastoma RAS (NRAS) repressors via specific stabilizing the RNA G-Quadruplex. J Med Chem. 2018;61(15):6629–6646. doi: 10.1021/acs.jmedchem.8b00257
  • Chen X-C, Tang G-X, Dai J, et al. Discovery of clinically used Octenidine as NRAS repressor that effectively inhibits NRAS -mutant melanoma. J Med Chem. 2023;66(7):5171–5184. doi: 10.1021/acs.jmedchem.3c00094
  • Adhikary S, Eilers M. Transcriptional regulation and transformation by myc proteins. Nat Rev Mol Cell Biol. 2005;6(8):635–645. doi: 10.1038/nrm1703
  • Pelengaris S, Khan M, Evan G. c-MYC: more than just a matter of life and death. Nat Rev Cancer. 2002;2(10):764–776. doi: 10.1038/nrc904
  • Mathsyaraja H, Eisenman RN. Parsing myc paralogs in oncogenesis. Cancer Cell. 2016;29(1):1–2. doi: 10.1016/j.ccell.2015.12.009
  • Dang CV, O’Donnell KA, Zeller KI, et al. The c-MYC target gene network. Semin Cancer Biol. 2006;16(4):253–264. doi: 10.1016/j.semcancer.2006.07.014
  • Meyer N, Penn LZ. Reflecting on 25 years with MYC. Nat Rev Cancer. 2008;8(12):976–990. doi: 10.1038/nrc2231
  • Blackwood EM, Eisenman RN. Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-Binding complex with myc. Science. 1991;251(4998):1211–1217. doi: 10.1126/science.2006410
  • Blackwood EM, Lüscher B, Eisenman RN. Myc and max associate in vivo. Genes Dev. 1992;6(1):71–80. doi: 10.1101/gad.6.1.71
  • Hurlin PJ, Quéva C, Eisenman RN. Mnt, a novel max-interacting protein is coexpressed with myc in proliferating cells and mediates repression at myc binding sites. Genes Dev. 1997;11(1):44–58. doi: 10.1101/gad.11.1.44
  • Nie Z, Hu G, Wei G, et al. c-MYC is a Universal Amplifier of expressed genes in Lymphocytes and embryonic stem cells. Cell. 2012;151(1):68–79. doi: 10.1016/j.cell.2012.08.033
  • Lin CY, Lovén J, Rahl PB, et al. Transcriptional amplification in tumor cells with elevated c-MYC. Cell. 2012;151(1):56–67. doi: 10.1016/j.cell.2012.08.026
  • Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–674. doi: 10.1016/j.cell.2011.02.013
  • Gabay M, Li Y, Felsher DW. MYC activation is a hallmark of cancer initiation and maintenance. Cold Spring Harb Perspect Med. 2014;4(6):a014241–a014241. doi: 10.1101/cshperspect.a014241
  • Felsher DW. MYC inactivation elicits oncogene addiction through both tumor cell-intrinsic and host-dependent mechanisms. Genes Cancer. 2010;1(6):597–604. doi: 10.1177/1947601910377798
  • Soucek L, Whitfield J, Martins CP, et al. Modelling myc inhibition as a cancer therapy. Nature. 2008;455(7213):679–683. doi: 10.1038/nature07260
  • Chen H, Liu H, Qing G. Targeting oncogenic myc as a strategy for cancer treatment. Signal Transduct Target Ther. 2018;3(1):1–7. doi: 10.1038/s41392-018-0008-7
  • González V, Hurley LH. The c- MYC NHE III 1: function and regulation. Annu Rev Pharmacol Toxicol. 2010;50(1):111–129. doi: 10.1146/annurev.pharmtox.48.113006.094649
  • Wang W, Hu S, Gu Y, et al. Human MYC G-quadruplex: from discovery to a cancer therapeutic target. Biochim Biophys Acta - Rev Cancer. 2020;1874(2):188410. doi: 10.1016/j.bbcan.2020.188410
  • Simonsson T, Pecinka P, Kubista M. DNA tetraplex formation in the control region of c-MYC. Nucleic Acids Res. 1998;26(5):1167–1172. doi: 10.1093/nar/26.5.1167
  • Siddiqui-Jain A, Grand CL, Bearss DJ, et al. Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription. Proc Natl Acad Sci U S A. 2002;99(18):11593–11598. doi: 10.1073/pnas.182256799
  • Phan AT, Modi YS, Patel DJ. Propeller-type parallel-stranded G-Quadruplexes in the human c-MYC promoter. J Am Chem Soc. 2004;126(28):8710–8716. doi: 10.1021/ja048805k
  • Ambrus A, Chen D, Dai J, et al. Solution structure of the biologically relevant G-Quadruplex element in the human c-MYC promoter. Implications for G-Quadruplex stabilization. Biochemistry. 2005;44(6):2048–2058. doi: 10.1021/bi048242p
  • Sun D, Hurley LH. The importance of negative superhelicity in inducing the formation of G-quadruplex and i-motif structures in the c-MYC promoter: implications for drug targeting and control of gene expression. J Med Chem. 2009;52(9):2863–2874. doi: 10.1021/jm900055s
  • Seenisamy J, Rezler EM, Powell TJ, et al. The dynamic character of the G-quadruplex element in the c-MYC promoter and modification by TMPyP4. J Am Chem Soc. 2004;126(28):8702–8709. doi: 10.1021/ja040022b
  • Chaudhuri R, Bhattacharya S, Dash J, et al. Recent update on targeting c-MYC G-Quadruplexes by small molecules for anticancer therapeutics. J Med Chem. 2021;64(1):42–70. doi: 10.1021/acs.jmedchem.0c01145
  • Zeng D-Y, Kuang G-T, Wang S-K, et al. Discovery of novel 11-triazole substituted Benzofuro[3,2- b]quinolone derivatives as c-myc G-Quadruplex specific stabilizers via Click chemistry. J Med Chem. 2017;60(13):5407–5423. doi: 10.1021/acs.jmedchem.7b00016
  • Wu T-Y, Chen X-C, Tang G-X, et al. Development and characterization of benzoselenazole derivatives as potent and selective c-MYC transcription inhibitors. J Med Chem. 2023;66(8):5484–5499. doi: 10.1021/acs.jmedchem.2c01808
  • Chen MC, Tippana R, Demeshkina NA, et al. Structural basis of G-quadruplex unfolding by the DEAH/RHA helicase DHX36. Nature. 2018;558(7710):465–469. doi: 10.1038/s41586-018-0209-9
  • Sengupta P, Bhattacharya A, Sa G, et al. Truncated G-quadruplex isomers cross-talk with the transcription factors to maintain homeostatic equilibria in c-MYC transcription. Biochemistry. 2019;58(15):1975–1991. doi: 10.1021/acs.biochem.9b00030
  • González V, Guo K, Hurley L, et al. Identification and characterization of nucleolin as a c-myc G-quadruplex-binding protein. J Biol Chem. 2009;284(35):23622–23635. doi: 10.1074/jbc.M109.018028
  • Fekete A, Kenesi E, Hunyadi-Gulyas E, et al. The guanine-quadruplex structure in the human c-myc gene’s promoter is converted into B-DNA form by the human Poly(ADP-Ribose)Polymerase-1. PLoS One. 2012;7:e42690. doi: 10.1371/journal.pone.0042690
  • Bossone SA, Asselin C, Patel AJ, et al. MAZ, a zinc finger protein, binds to c-MYC and C2 gene sequences regulating transcriptional initiation and termination. Proc Natl Acad Sci. 1992;89(16):7452–7456. doi: 10.1073/pnas.89.16.7452
  • Lacombe ML, Milon L, Munier A, et al. The human Nm23/nucleoside diphosphate kinases. J Bioenerg Biomembr. 2000;32(3):247–258. doi: 10.1023/A:1005584929050
  • Postel EH, Berberich SJ, Flint SJ, et al. Human c- myc transcription factor PuF identified as nm23-H2 nucleoside diphosphate kinase, a candidate suppressor of tumor metastasis. Science (80). 1993;261(5120):478–480. doi: 10.1126/science.8392752
  • Dexheimer TS, Carey SS, Zuohe S, et al. NM23-H2 may play an indirect role in transcriptional activation of c-myc gene expression but does not cleave the nuclease hypersensitive element III1. Mol Cancer Ther. 2009;8(5):1363–1377. doi: 10.1158/1535-7163.MCT-08-1093
  • Ginisty H, Sicard H, Roger B, et al. Structure and functions of nucleolin. J Cell Sci. 1999;112(6):761–772. doi: 10.1242/jcs.112.6.761
  • Tajrishi MM, Tuteja R, Tuteja N. Nucleolin. Commun Integr Biol. 2011;4:267–275. doi:10.4161/cib.4.3.14884
  • González V, Hurley LH. The C-terminus of nucleolin promotes the formation of the c-MYC G-quadruplex and inhibits c-MYC promoter activity. Biochemistry. 2010;49(45):9706–9714. doi: 10.1021/bi100509s
  • Yarden Y, Kuang WJ, Yang-Feng T, et al. Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. EMBO J. 1987;6(11):3341–3351. doi: 10.1002/j.1460-2075.1987.tb02655.x
  • Liang J, Wu Y-L, Chen B-J, et al. The C-Kit receptor-mediated signal transduction and tumor-related diseases. Int J Biol Sci. 2013;9(5):435–443. doi: 10.7150/ijbs.6087
  • Rubin BP, Heinrich MC, Corless CL. Gastrointestinal stromal tumour. Lancet. 2007;369(9574):1731–1741. doi: 10.1016/S0140-6736(07)60780-6
  • Genomic and epigenomic landscapes of adult De novo acute myeloid leukemia. N Engl J Med. 2013;368(22):2059–2074. doi: 10.1056/NEJMoa1301689
  • Kim H-J, Ahn HK, Jung CW, et al. KIT D816 mutation associates with adverse outcomes in core binding factor acute myeloid leukemia, especially in the subgroup with RUNX1/RUNX1T1 rearrangement. Ann Hematol. 2013;92(2):163–171. doi: 10.1007/s00277-012-1580-5
  • Curtin JA, Busam K, Pinkel D, et al. Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol. 2006;24(26):4340–4346. doi: 10.1200/JCO.2006.06.2984
  • Rankin S, Reszka AP, Huppert J, et al. Putative DNA quadruplex formation within the human c-kit oncogene. J Am Chem Soc. 2005;127(30):10584–10589. doi: 10.1021/ja050823u
  • Fernando H, Reszka AP, Huppert J, et al. A conserved quadruplex motif located in a transcription activation site of the human c-kit oncogene. Biochemistry. 2006;45(25):7854–7860. doi: 10.1021/bi0601510
  • Raiber E-A, Kranaster R, Lam E, et al. A non-canonical DNA structure is a binding motif for the transcription factor SP1 in vitro. Nucleic Acids Res. 2012;40(4):1499–1508. doi: 10.1093/nar/gkr882
  • Deniaud E, Baguet J, Chalard R, et al. Overexpression of transcription factor Sp1 leads to gene expression perturbations and cell cycle inhibition. PLoS One. 2009;4(9):e7035. doi: 10.1371/journal.pone.0007035
  • Phan AT, Kuryavyi V, Burge S, et al. Structure of an unprecedented G-quadruplex scaffold in the human c-kit promoter. J Am Chem Soc. 2007;129(14):4386–4392. doi: 10.1021/ja068739h
  • Phan AT, Kuryavyi V, Gaw HY, et al. Small-molecule interaction with a five-guanine-tract G-quadruplex structure from the human MYC promoter. Nat Chem Biol. 2005;1(3):167–173. doi: 10.1038/nchembio723
  • Wei D, Parkinson GN, Reszka AP, et al. Crystal structure of a c-kit promoter quadruplex reveals the structural role of metal ions and water molecules in maintaining loop conformation. Nucleic Acids Res. 2012;40(10):4691–4700. doi: 10.1093/nar/gks023
  • Hsu S-T, Varnai P, Bugaut A, et al. A G-Rich sequence within the c-kit oncogene promoter forms a parallel G-Quadruplex having asymmetric G-tetrad dynamics. J Am Chem Soc. 2009;131(37):13399–13409. doi: 10.1021/ja904007p
  • Kuryavyi V, Phan AT, Patel DJ. Solution structures of all parallel-stranded monomeric and dimeric G-quadruplex scaffolds of the human c-kit2 promoter. Nucleic Acids Res. 2010;38(19):6757–6773. doi: 10.1093/nar/gkq558
  • Kotar A, Rigo R, Sissi C, et al. Two-quartet kit* G-quadruplex is formed via double-stranded pre-folded structure. Nucleic Acids Res. 2019;47(5):2641–2653. doi: 10.1093/nar/gky1269
  • Bignon E, Spinello A, Miclot T, et al. Predicting the three-dimensional structure of the c- KIT proto-oncogene promoter and the dynamics of its strongly coupled guanine quadruplexes. J Phys Chem Lett. 2023;14(20):4704–4710. doi: 10.1021/acs.jpclett.3c00765
  • Da Ros S, Nicoletto G, Rigo R, et al. G-Quadruplex modulation of SP1 functional binding sites at the KIT proximal promoter. Int J Mol Sci. 2020;22(1):329. doi: 10.3390/ijms22010329
  • Zorzan E, Elgendy R, Giantin M, et al. Whole-transcriptome profiling of canine and human in vitro models exposed to a G-quadruplex binding small molecule. Sci Rep. 2018;8(1):17107. doi: 10.1038/s41598-018-35516-y
  • Bejugam M, Sewitz S, Shirude PS, et al. Trisubstituted isoalloxazines as a New class of G-Quadruplex binding ligands: small molecule regulation of c-kit oncogene expression. J Am Chem Soc. 2007;129(43):12926–12927. doi: 10.1021/ja075881p
  • Gunaratnam M, Swank S, Haider SM, et al. Targeting human gastrointestinal stromal tumor cells with a quadruplex-binding small molecule. J Med Chem. 2009;52(12):3774–3783. doi: 10.1021/jm900424a
  • Bejugam M, Gunaratnam M, Müller S, et al. Targeting the c-kit promoter G-quadruplexes with 6-substituted indenoisoquinolines. ACS Med Chem Lett. 2010;1(7):306–310. doi: 10.1021/ml100062z
  • McLuckie KIE, Waller ZAE, Sanders DA, et al. G-Quadruplex-binding benzo[a]phenoxazines down-regulate c-KIT expression in human gastric carcinoma cells. J Am Chem Soc. 2011;133(8):2658–2663. doi: 10.1021/ja109474c
  • Waller ZAE, Sewitz SA, Hsu S-T, et al. A small molecule that disrupts G-Quadruplex DNA structure and enhances gene expression. J Am Chem Soc. 2009;131(35):12628–12633. doi: 10.1021/ja901892u
  • Wang X, Zhou C-X, Yan J-W, et al. Synthesis and evaluation of quinazolone derivatives as a New class of c - KIT G-quadruplex binding ligands. ACS Med Chem Lett. 2013;4(10):909–914. doi: 10.1021/ml400271y
  • Zorzan E, Ros Da S, Musetti C, et al. Screening of candidate G-quadruplex ligands for the human c-KIT promotorial region and their effects in multiple in-vitro models. Oncotarget. 2016;7(16):21658–21675. doi: 10.18632/oncotarget.7808
  • Paul R, Dutta D, Das T, et al. G4 sensing pyridyl‐thiazole polyamide represses c‐KIT expression in leukemia cells. Chem A Eur J. 2021;27(33):8590–8599. doi: 10.1002/chem.202100907
  • Soldatenkov VA, Vetcher AA, Duka T, et al. First evidence of a functional interaction between DNA quadruplexes and poly(ADP-ribose) polymerase-1. ACS Chem Biol. 2008;3(4):214–219. doi: 10.1021/cb700234f
  • Edwards AD, Marecki JC, Byrd AK, et al. G-quadruplex loops regulate PARP-1 enzymatic activation. Nucleic Acids Res. 2021;49(1):416–431. doi: 10.1093/nar/gkaa1172
  • Meier-Stephenson V. G4-quadruplex-binding proteins: review and insights into selectivity. Biophys Rev. 2022;14(3):635–654. doi: 10.1007/s12551-022-00952-8
  • Lago S, Tosoni E, Nadai M, et al. The cellular protein nucleolin preferentially binds long-looped G-quadruplex nucleic acids. Biochim Biophys Acta - Gen Subj. 2017;1861(5):1371–1381. doi: 10.1016/j.bbagen.2016.11.036
  • Hockenbery D, Nuñez G, Milliman C, et al. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature. 1990;348(6299):334–336. doi: 10.1038/348334a0
  • Wei Y, Pattingre S, Sinha S, et al. JNK1-mediated phosphorylation of bcl-2 regulates starvation-induced autophagy. Mol Cell. 2008;30(6):678–688. doi: 10.1016/j.molcel.2008.06.001
  • Strappazzon F, Vietri-Rudan M, Campello S, et al. Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy. EMBO J. 2011;30(7):1195–1208. doi: 10.1038/emboj.2011.49
  • Chen D, Gao F, Li B, et al. Parkin Mono-ubiquitinates bcl-2 and regulates autophagy. J Biol Chem. 2010;285(49):38214–38223. doi: 10.1074/jbc.M110.101469
  • Radha G, Raghavan SC. BCL2: a promising cancer therapeutic target. Biochim Biophys Acta - Rev Cancer. 2017;1868(1):309–314. doi: 10.1016/j.bbcan.2017.06.004
  • Oltersdorf T, Elmore SW, Shoemaker AR, et al. An inhibitor of bcl-2 family proteins induces regression of solid tumours. Nature. 2005;435(7042):677–681. doi: 10.1038/nature03579
  • Seto M, Jaeger U, Hockett RD, et al. Alternative promoters and exons, somatic mutation and deregulation of the bcl-2-Ig fusion gene in lymphoma. EMBO J. 1988;7(1):123–131. doi: 10.1002/j.1460-2075.1988.tb02791.x
  • Young RL, Korsmeyer SJ. A negative regulatory element in the bcl-2 5’-untranslated region inhibits expression from an upstream promoter. Mol Cell Biol. 1993;13(6):3686–3697. doi: 10.1128/MCB.13.6.3686
  • Dexheimer TS, Sun D, Hurley LH. Deconvoluting the structural and drug-recognition complexity of the G-quadruplex-forming region upstream of the bcl-2 P1 promoter. J Am Chem Soc. 2006;128(16):5404–5415. doi: 10.1021/ja0563861
  • Onel B, Carver M, Wu G, et al. A New G-quadruplex with hairpin loop immediately upstream of the human BCL2 P1 promoter modulates transcription. J Am Chem Soc. 2016;138(8):2563–2570. doi: 10.1021/jacs.5b08596
  • Dai J, Chen D, Jones RA, et al. NMR solution structure of the major G-quadruplex structure formed in the human BCL2 promoter region. Nucleic Acids Res. 2006;34(18):5133–5144. doi: 10.1093/nar/gkl610
  • Dai J, Dexheimer TS, Chen D, et al. An intramolecular G-Quadruplex structure with mixed parallel/antiparallel G-strands formed in the human BCL-2 promoter region in solution. J Am Chem Soc. 2006;128(4):1096–1098. doi: 10.1021/ja055636a
  • Agrawal P, Lin C, Mathad RI, et al. The major G-Quadruplex formed in the human BCL-2 proximal promoter adopts a parallel structure with a 13-nt loop in K + solution. J Am Chem Soc. 2014;136(5):1750–1753. doi: 10.1021/ja4118945
  • Chen L, Dickerhoff J, Sakai S, et al. DNA G-Quadruplex in human telomeres and oncogene promoters: structures, functions, and small molecule targeting. Acc Chem Res. 2022;55(18):2628–2646. doi: 10.1021/acs.accounts.2c00337
  • Sun H, Xiang J, Shi Y, et al. A newly identified G-quadruplex as a potential target regulating bcl-2 expression. Biochim Biophys Acta - Gen Subj. 2014;1840(10):3052–3057. doi: 10.1016/j.bbagen.2014.07.014
  • Mayo MW, Wang C-Y, Drouin SS, et al. WT1 modulates apoptosis by transcriptionally upregulating the bcl-2 proto-oncogene. EMBO J. 1999;18(14):3990–4003. doi: 10.1093/emboj/18.14.3990
  • Ji L, Mochon E, Arcinas M, et al. CREB proteins function as positive regulators of the translocated -2 allele in t(14;18) lymphomas. J Biol Chem. 1996;271(37):22687–22691. doi: 10.1074/jbc.271.37.22687
  • Gomez-Manzano C, Mitlianga P, Fueyo J, et al. Transfer of E2F-1 to human glioma cells results in transcriptional up-regulation of bcl-2. Cancer Res. 2001;61(18):6693–6697.
  • Heckman CA, Mehew JW, Boxer LM. NF-κB activates bcl-2 expression in t(14;18) lymphoma cells. Oncogene. 2002;21(24):3898–3908. doi: 10.1038/sj.onc.1205483
  • Liu Y-Z, Boxer LM, Latchman DS. Activation of the bcl-2 promoter by nerve growth factor is mediated by the p42/p44 MAPK cascade. Nucleic Acids Res. 1999;27(10):2086–2090. doi: 10.1093/nar/27.10.2086
  • Heckman C, Mochon E, Arcinas M, et al. The WT1 protein is a negative regulator of the normalbcl-2 allele in t(14;18) lymphomas. J Biol Chem. 1997;272(31):19609–19614. doi: 10.1074/jbc.272.31.19609
  • Xiong Y-X, Chen A-C, Yao P-F, et al. Blocking the binding of WT1 to bcl-2 promoter by G-quadruplex ligand SYUIQ-FM05. Biochem Biophys Reports. 2016;5:346–352. doi: 10.1016/j.bbrep.2015.12.014
  • Le VH, Nagesh N, Lewis EA, et al. Bcl-2 promoter sequence G-Quadruplex interactions with three planar and non-planar cationic porphyrins: TMPyP4, TMPyP3, and TMPyP2. PLoS One. 2013;8(8):e72462. doi: 10.1371/journal.pone.0072462
  • Sheu S-Y, Huang C-H, Zhou J-K, et al. Relative stability of G-quadruplex structures: interactions between the human Bcl2 promoter region and derivatives of carbazole and diphenylamine. Biopolymers. 2014;101(10):1038–1050. doi: 10.1002/bip.22497
  • Feng Y, Yang D, Chen H, et al. Stabilization of G-quadruplex DNA and inhibition of bcl-2 expression by a pyridostatin analog. Bioorg Med Chem Lett. 2016;26(7):1660–1663. doi: 10.1016/j.bmcl.2016.02.065
  • Jana J, Mondal S, Bhattacharjee P, et al. Chelerythrine down regulates expression of VEGFA, BCL2 and KRAS by arresting G-Quadruplex structures at their promoter regions. Sci Rep. 2017;7(1):40706. doi: 10.1038/srep40706
  • Gunaratnam M, Collie GW, Reszka AP, et al. A naphthalene diimide G-quadruplex ligand inhibits cell growth and down-regulates BCL-2 expression in an imatinib-resistant gastrointestinal cancer cell line. Bioorg Med Chem. 2018;26(11):2958–2964. doi: 10.1016/j.bmc.2018.04.050
  • Wang X, Zhang M, Xiong X-Q, et al. Design, synthesis and bioactivity of novel naphthalimide-benzotriazole conjugates against A549 cells via targeting BCL2 G-quadruplex and inducing autophagy. Life Sci. 2022;302:120651. doi: 10.1016/j.lfs.2022.120651
  • Amato J, Pagano A, Capasso D, et al. Targeting the BCL2 gene promoter G-Quadruplex with a New class of furopyridazinone-based molecules. ChemMedchem. 2018;13(5):406–410. doi: 10.1002/cmdc.201700749
  • Castillo-Gonzalez D, Perez-Machado G, Guedin A, et al. FDA-approved drugs selected using virtual screening bind specifically to G-quadruplex DNA. Curr Pharm Des. 2013;19(12):2164–2173. doi: 10.2174/1381612811319120004
  • Pandya N, Jain N, Kumar A. Interaction analysis of anti-cancer drug methotrexate with bcl-2 promoter stabilization and its transcription regulation. Gene Rep. 2021;23:101155. doi:10.1016/j.genrep.2021.101155
  • Kendrick S, Akiyama Y, Hecht SM, et al. The i-motif in the bcl-2 P1 promoter forms an unexpectedly stable structure with a unique 8: 5: 7 loop folding pattern. J Am Chem Soc. 2009;131(48):17667–17676. doi: 10.1021/ja9076292
  • Amato J, Iaccarino N, D’Aria F, et al. Conformational plasticity of DNA secondary structures: probing the conversion between i-motif and hairpin species by circular dichroism and ultraviolet resonance Raman spectroscopies. Phys Chem Chem Phys. 2022;24(11):7028–7044. doi: 10.1039/D2CP00058J
  • Kang HJ, Kendrick S, Hecht SM, et al. The transcriptional complex between the BCL2 i-motif and hnRNP LL is a molecular switch for control of gene expression that can be modulated by small molecules. J Am Chem Soc. 2014;136(11):4172–4185. doi: 10.1021/ja4109352
  • Cong Y-S, Wright WE, Shay JW. Human telomerase and its regulation. Microbiol Mol Biol Rev. 2002;66(3):407–425. doi: 10.1128/MMBR.66.3.407-425.2002
  • Greider CW, Blackburn EH. The telomere terminal transferase of tetrahymena is a ribonucleoprotein enzyme with two kinds of primer specificity. Cell. 1987;51(6):887–898. doi: 10.1016/0092-8674(87)90576-9
  • Feng J, Funk WD, Wang S-S, et al. The RNA component of human telomerase. Science (80). 1995;269(5228):1236–1241. doi: 10.1126/science.7544491
  • Wright WE, Piatyszek MA, Rainey WE, et al. Telomerase activity in human germline and embryonic tissues and cells. Dev Genet. 1996;18(2):173–179. doi: 10.1002/(SICI)1520-6408(1996)18:2<173:AID-DVG10>3.0.CO;2-3
  • Izbicka E, Wheelhouse RT, Raymond E, et al. Effects of cationic porphyrins as G-quadruplex interactive agents in human tumor cells. Cancer Res. 1999;59(3):639–644.
  • Shay JW, Bacchetti S. A survey of telomerase activity in human cancer. Eur J Cancer. 1997;33(5):787–791. doi: 10.1016/S0959-8049(97)00062-2
  • Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990;345(6274):458–460. doi: 10.1038/345458a0
  • Kim NW, Piatyszek MA, Prowse KR, et al. Specific association of human telomerase activity with immortal cells and cancer. Science (80). 1994;266(5193):2011–2015. doi: 10.1126/science.7605428
  • Nakamura TM, Morin GB, Chapman KB, et al. Telomerase catalytic subunit homologs from fission yeast and human. Science (80). 1997;277(5328):955–959. doi: 10.1126/science.277.5328.955
  • Counter CM, Meyerson M, Eaton EN, et al. Telomerase activity is restored in human cells by ectopic expression of hTERT (hEST2), the catalytic subunit of telomerase. Oncogene. 1998;16(9):1217–1222. doi: 10.1038/sj.onc.1201882
  • Cong Y. The human telomerase catalytic subunit hTERT: organization of the gene and characterization of the promoter. Hum Mol Genet. 1999;8(1):137–142. doi: 10.1093/hmg/8.1.137
  • Horikawa I, Cable PL, Afshari C, et al. Cloning and characterization of the promoter region of human telomerase reverse transcriptase gene. Cancer Res. 1999;59(4):826–830.
  • Takakura M, Kyo S, Kanaya T, et al. Cloning of human telomerase catalytic subunit (hTERT) gene promoter and identification of proximal core promoter sequences essential for transcriptional activation in immortalized and cancer cells. Cancer Res. 1999;59(3):551–557.
  • Wu K-J, Grandori C, Amacker M, et al. Direct activation of TERT transcription by c-MYC. Nat Genet. 1999;21(2):220–224. doi: 10.1038/6010
  • Palumbo SL, Ebbinghaus SW, Hurley LH. Formation of a unique end-to-end stacked pair of G-quadruplexes in the hTERT Core promoter with implications for inhibition of telomerase by G-Quadruplex-interactive ligands. J Am Chem Soc. 2009;131(31):10878–10891. doi: 10.1021/ja902281d
  • Micheli E, Martufi M, Cacchione S, et al. Self-organization of G-quadruplex structures in the hTERT core promoter stabilized by polyaminic side chain perylene derivatives. Biophys Chem. 2010;153(1):43–53. doi: 10.1016/j.bpc.2010.10.003
  • Lim KW, Lacroix L, Yue DJE, et al. Coexistence of two distinct G-Quadruplex conformations in the hTERT Promoter. J Am Chem Soc. 2010;132(35):12331–12342. doi: 10.1021/ja101252n
  • Kang H-J, Cui Y, Yin H, et al. A pharmacological Chaperone molecule induces cancer cell death by restoring tertiary DNA structures in mutant hTERT Promoters. J Am Chem Soc. 2016;138(41):13673–13692. doi: 10.1021/jacs.6b07598
  • Monsen RC, DeLeeuw L, Dean WL, et al. The hTERT core promoter forms three parallel G-quadruplexes. Nucleic Acids Res. 2020;48(10):5720–5734. doi: 10.1093/nar/gkaa107
  • Chaires JB, Trent JO, Gray RD, et al. An improved model for the hTERT Promoter quadruplex. PLoS One. 2014;9(12):e115580. doi: 10.1371/journal.pone.0115580
  • Bentham Science Publisher BSP, Bentham Science Publisher BSP. Telomerase inhibition in cancer therapeutics: molecular-based approaches. CMC. 2006;13(24):2875–2888. doi: 10.2174/092986706778521887
  • Mengual Gomez DL, Armando RG, Cerrudo CS, et al. Telomerase as a cancer target. Development of New molecules. Curr Top Med Chem. 2016;16(22):2432–2440. doi: 10.2174/1568026616666160212122425
  • Vo T, Oxenford S, Angell R, et al. Substituted Naphthalenediimide Compounds Bind Selectively to Two Human Quadruplex Structures with Parallel Topology. ACS Med Chem Lett. 2020;11(5):991–999. doi: 10.1021/acsmedchemlett.0c00041
  • Song JH, Kang H-J, Luevano LA, et al. Small-molecule-targeting hairpin loop of hTERT Promoter G-Quadruplex induces cancer cell death. Cell Chem Biol. 2019;26(8):1110–1121.e4. doi: 10.1016/j.chembiol.2019.04.009
  • Sharma S, Mukherjee AK, Roy SS, et al. Human telomerase is directly regulated by non-telomeric TRF2-G-quadruplex interaction. Cell Rep. 2021;35(7):109154. doi: 10.1016/j.celrep.2021.109154
  • Yamazaki Y, Morita T. Molecular and functional diversity of vascular endothelial growth factors. Mol Divers. 2006;10(4):515. doi: 10.1007/s11030-006-9027-3
  • Senger DR, Galli SJ, Dvorak AM, et al. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983;219(4587):983–985. doi: 10.1126/science.6823562
  • Carmeliet P, Ferreira V, Breier G, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature. 1996;380(6573):435–439. doi: 10.1038/380435a0
  • Goede V, Schmidt T, Kimmina S, et al. Analysis of blood vessel maturation processes during cyclic ovarian angiogenesis. Lab Invest. 1998;78(11):1385–1394.
  • Thomas KA. Vascular endothelial growth factor, a potent and selective angiogenic agent. J Biol Chem. 1996;271(2):603–606. doi: 10.1074/jbc.271.2.603
  • Ferrara N. Vascular endothelial growth factor as a target for anticancer therapy. Oncology. 2004;9(S1):2–10. doi: 10.1634/theoncologist.9-suppl_1-2
  • Onesto C, Berra E, Grépin R, et al. Poly(a)-binding protein-interacting protein 2, a strong regulator of vascular endothelial growth factor mRNA. J Biol Chem. 2004;279(33):34217–34226. doi: 10.1074/jbc.M400219200
  • Huez I, Créancier L, Audigier S, et al. Two independent internal ribosome entry sites are involved in translation initiation of vascular endothelial growth factor mRNA. Mol Cell Biol. 1998;18(11):6178–6190. doi: 10.1128/MCB.18.11.6178
  • Shweiki D, Itin A, Soffer D, et al. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature. 1992;359(6398):843–845. doi: 10.1038/359843a0
  • Pal S, Datta K, Mukhopadhyay D. Central role of p53 on regulation of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) expression in mammary carcinoma. Cancer Res. 2001;61(18):6952–6957.
  • Grugel S, Finkenzeller G, Weindel K, et al. Both v-Ha-ras and v-Raf stimulate expression of the vascular endothelial growth factor in NIH 3T3 cells. J Biol Chem. 1995;270(43):25915–25919. doi: 10.1074/jbc.270.43.25915
  • Cohen T, Nahari D, Cerem LW, et al. Interleukin 6 induces the expression of vascular endothelial growth factor. J Biol Chem. 1996;271(2):736–741. doi: 10.1074/jbc.271.2.736
  • Shi Q, Le X, Abbruzzese JL, et al. Constitutive Sp1 activity is essential for differential constitutive expression of vascular endothelial growth factor in human pancreatic adenocarcinoma. Cancer Res. 2001;61(10):4143–4154.
  • Guo K, Gokhale V, Hurley LH, et al. Intramolecularly folded G-quadruplex and i-motif structures in the proximal promoter of the vascular endothelial growth factor gene. Nucleic Acids Res. 2008;36(14):4598–4608. doi: 10.1093/nar/gkn380
  • Sun D. Facilitation of a structural transition in the polypurine/polypyrimidine tract within the proximal promoter region of the human VEGF gene by the presence of potassium and G-quadruplex-interactive agents. Nucleic Acids Res. 2005;33(18):6070–6080. doi: 10.1093/nar/gki917
  • Sun D, Liu W-J, Guo K, et al. The proximal promoter region of the human vascular endothelial growth factor gene has a G-quadruplex structure that can be targeted by G-quadruplex–interactive agents. Mol Cancer Ther. 2008;7(4):880–889. doi: 10.1158/1535-7163.MCT-07-2119
  • Agrawal P, Hatzakis E, Guo K, et al. Solution structure of the major G-quadruplex formed in the human VEGF promoter in K+: insights into loop interactions of the parallel G-quadruplexes. Nucleic Acids Res. 2013;41(22):10584–10592. doi: 10.1093/nar/gkt784
  • Gasparini G, Bonoldi E, Gatti C, et al. Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma. JNCI J Natl Cancer Inst. 1997;89(2):139–147. doi: 10.1093/jnci/89.2.139
  • De Paola F, Granato AM, Scarpi E, et al. Vascular endothelial growth factor and prognosis in patients with node-negative breast cancer. Int J Cancer. 2002;98(2):228–233. doi: 10.1002/ijc.10118
  • Ellis LM, Takahashi Y, Liu W, et al. Vascular endothelial growth factor in human colon cancer: biology and therapeutic implications. Oncology. 2000;5(S1):11–15. doi: 10.1634/theoncologist.5-suppl_1-11
  • Lee J-C, Chow N-H, Wang S-T, et al. Prognostic value of vascular endothelial growth factor expression in colorectal cancer patients. Eur J Cancer. 2000;36(6):748–753. doi: 10.1016/S0959-8049(00)00003-4
  • Shen GH, Ghazizadeh M, Kawanami O, et al. Prognostic significance of vascular endothelial growth factor expression in human ovarian carcinoma. Br J Cancer. 2000;83(2):196–203. doi: 10.1054/bjoc.2000.1228
  • Harris AL, O’Byrne KJ, Dobbs N, et al. Vascular endothelial growth factor platelet counts, and prognosis in renal cancer. Lancet. 1999;353(9163):1494–1495. doi: 10.1016/S0140-6736(99)00471-7
  • CHENG W. Vascular endothelial growth factor in cervical carcinoma. Obstet Gynecol. 1999;93(5):761–765. doi: 10.1016/S0029-7844(98)00505-5
  • Mineta H, Miura K, Ogino T, et al. Prognostic value of vascular endothelial growth factor (VEGF) in head and neck squamous cell carcinomas. Br J Cancer. 2000;83(6):775–781. doi: 10.1054/bjoc.2000.1357
  • Taka T, Joonlasak K, Huang L, et al. Down-regulation of the human VEGF gene expression by perylene monoimide derivatives. Bioorg Med Chem Lett. 2012;22(1):518–522. doi: 10.1016/j.bmcl.2011.10.089
  • Wu Y, Zan L-P, Wang X-D, et al. Stabilization of VEGF G-quadruplex and inhibition of angiogenesis by quindoline derivatives. Biochim Biophys Acta - Gen Subj. 2014;1840(9):2970–2977. doi: 10.1016/j.bbagen.2014.06.002
  • Bhattacharjee S, Chakraborty S, Chorell E, et al. Importance of the hydroxyl substituents in the B–ring of plant flavonols on their preferential binding interactions with VEGF G–quadruplex DNA: multi-spectroscopic and molecular modeling studies. Int j biol macromol. 2018;118:629–639. doi: 10.1016/j.ijbiomac.2018.06.115
  • Bhattacharjee S, Sengupta PK, Bhowmik S. Exploring the preferential interaction of quercetin with VEGF promoter G-quadruplex DNA and construction of a pH-dependent DNA-based logic gate. RSC Adv. 2017;7(59):37230–37240. doi: 10.1039/C7RA05930B
  • Heldin C-H, Westermark B. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev. 1999;79(4):1283–1316. doi: 10.1152/physrev.1999.79.4.1283
  • Heldin C-H, Eriksson U, Östman A. New members of the platelet-derived growth factor family of mitogens. Arch Biochem Biophys. 2002;398(2):284–290. doi: 10.1006/abbi.2001.2707
  • Alvarez RH, Kantarjian HM, Cortes JE. Biology of platelet-derived growth factor and its involvement in disease. Mayo Clin Proc. 2006;81(9):1241–1257. doi: 10.4065/81.9.1241
  • Betsholtz C. Biology of platelet-derived growth factors in development. Birth Defects Res Part C Embryo Today Rev. 2003;69(4):272–285. doi: 10.1002/bdrc.10030
  • Yu J, Ustach C, ChoiKim H-R. Platelet-derived growth factor signaling and human cancer. BMB Rep. 2003;36(1):49–59. doi: 10.5483/BMBRep.2003.36.1.049
  • Westermark B, Heldin C, Nistér M. Platelet‐derived growth factor in human glioma. Glia. 1995;15(3):257–263. doi: 10.1002/glia.440150307
  • Sulzbacher I, Birner P, Trieb K, et al. Expression of platelet-derived growth factor-AA is associated with tumor progression in Osteosarcoma. Mod Pathol. 2003;16(1):66–71. doi: 10.1097/01.MP.0000043522.76788.0A
  • Guha A, Dashner K, Mc Black PL, et al. Expression of PDGF and PDGF receptors in human astrocytoma operation specimens supports the existence of an autocrine loop. Int J Cancer. 1995;60(2):168–173. doi: 10.1002/ijc.2910600206
  • Qin Y, Rezler EM, Gokhale V, et al. Characterization of the G-quadruplexes in the duplex nuclease hypersensitive element of the PDGF-A promoter and modulation of PDGF-A promoter activity by TMPyP4. Nucleic Acids Res. 2007;35(22):7698–7713. doi: 10.1093/nar/gkm538
  • Kaetzel DM. Transcription of the platelet-derived growth factor A-chain gene. Cytokine Growth Factor Rev. 2003;14(5):427–446. doi: 10.1016/S1359-6101(03)00051-0
  • Silverman ES, Khachigian LM, Lindner V, et al. Inducible PDGF A-chain transcription in smooth muscle cells is mediated by Egr-1 displacement of Sp1 and Sp3. Am J Physiol Circ Physiol. 1997;273(3):H1415–26. doi: 10.1152/ajpheart.1997.273.3.H1415
  • Gashler AL, Bonthron DT, Madden SL, et al. Human platelet-derived growth factor a chain is transcriptionally repressed by the Wilms tumor suppressor WT1. Proc Natl Acad Sci. 1992;89(22):10984–10988. doi: 10.1073/pnas.89.22.10984
  • Wang ZY, Madden SL, Deuel TF, et al. The Wilms’ tumor gene product, WT1, represses transcription of the platelet-derived growth factor A-chain gene. J Biol Chem. 1992;267(31):21999–22002. doi: 10.1016/S0021-9258(18)41624-9
  • Khachigian LM, Santiago FS, Rafty LA, et al. GC factor 2 represses platelet-derived growth factor A-Chain gene transcription and is Itself induced by arterial injury. Circ Res. 1999;84(11):1258–1267. doi: 10.1161/01.RES.84.11.1258
  • Rafty LA, Santiago FS, Khachigian LM. NF1/X represses PDGF A-chain transcription by interacting with Sp1 and antagonizing Sp1 occupancy of the promoter. EMBO J. 2002;21(3):334–343. doi: 10.1093/emboj/21.3.334
  • Ma D, Xing Z, Liu B, et al. NM23-H1 and NM23-H2 repress transcriptional activities of nuclease-hypersensitive elements in the platelet-derived growth factor-A promoter. J Biol Chem. 2002;277(2):1560–1567. doi: 10.1074/jbc.M108359200
  • Betsholtz C, Karlsson L, Lindahl P. Developmental roles of platelet-derived growth factors. BioEssays. 2001;23(6):494–507. doi: 10.1002/bies.1069
  • Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev. 2008;22(10):1276–1312. doi: 10.1101/gad.1653708
  • Östman A. PDGF receptors-mediators of autocrine tumor growth and regulators of tumor vasculature and stroma. Cytokine Growth Factor Rev. 2004;15(4):275–286. doi: 10.1016/j.cytogfr.2004.03.002
  • Furuhashi M, Sjöblom T, Abramsson A, et al. Platelet-derived growth factor production by B16 melanoma cells leads to increased pericyte abundance in tumors and an associated increase in tumor growth rate. Cancer Res. 2004;64(8):2725–2733. doi: 10.1158/0008-5472.CAN-03-1489
  • Coluccia AML, Cirulli T, Neri P, et al. Validation of PDGFRβ and c-src tyrosine kinases as tumor/vessel targets in patients with multiple myeloma: preclinical efficacy of the novel, orally available inhibitor dasatinib. Blood. 2008;112(4):1346–1356. doi: 10.1182/blood-2007-10-116590
  • Qin Y, Fortin JS, Tye D, et al. Molecular Cloning of the human platelet-derived growth factor receptor β (PDGFR-β) promoter and drug targeting of the G-Quadruplex-forming region to repress PDGFR-β expression. Biochemistry. 2010;49(19):4208–4219. doi: 10.1021/bi100330w
  • Chen Y, Agrawal P, Brown RV, et al. The major G-Quadruplex formed in the human platelet-derived growth factor receptor β promoter adopts a novel Broken-strand structure in K + solution. J Am Chem Soc. 2012;134(32):13220–13223. doi: 10.1021/ja305764d
  • Onel B, Carver M, Agrawal P, et al. The 3´-end region of the human PDGFR-β core promoter nuclease hypersensitive element forms a mixture of two unique end-insertion G-quadruplexes. Biochim Biophys Acta - Gen Subj. 2018;1862(4):846–854. doi: 10.1016/j.bbagen.2017.12.011
  • Bryan TM, Jarstfer MB. Interrogation of G-quadruplex–protein interactions. Methods. 2007;43(4):332–339. doi: 10.1016/j.ymeth.2007.05.001
  • Sissi C, Gatto B, Palumbo M. The evolving world of protein-G-quadruplex recognition: a medicinal chemist’s perspective. Biochimie. 2011;93(8):1219–1230. doi: 10.1016/j.biochi.2011.04.018
  • Brown RV, Wang T, Chappeta VR, et al. The consequences of overlapping G-quadruplexes and i-motifs in the platelet-derived growth factor receptor β core promoter nuclease hypersensitive element can explain the unexpected effects of mutations and provide opportunities for selective targeting of both structures by small molecules to downregulate gene expression. J Am Chem Soc. 2017;139(22):7456–7475. doi: 10.1021/jacs.6b10028
  • Gibson BA, Kraus WL. New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs. Nat Rev Mol Cell Biol. 2012;13(7):411–424. doi: 10.1038/nrm3376
  • Langelier M-F, Planck JL, Roy S, et al. Structural basis for DNA damage–dependent poly(ADP-ribosyl)ation by human PARP-1. Science (80). 2012;336(6082):728–732. doi: 10.1126/science.1216338
  • Ray Chaudhuri A, Nussenzweig A. The multifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nat Rev Mol Cell Biol. 2017;18(10):610–621. doi: 10.1038/nrm.2017.53
  • Fu H, Liu R, Jia Z, et al. Poly(adp-ribosylation) of P-TEFb by PARP1 disrupts phase separation to inhibit global transcription after DNA damage. Nat Cell Biol. 2022;24(4):513–525. doi: 10.1038/s41556-022-00872-5
  • Ossovskaya V, Koo IC, Kaldjian EP, et al. Upregulation of poly (ADP-Ribose) polymerase-1 (PARP1) in triple-negative breast cancer and other primary human tumor types. Genes Cancer. 2010;1(8):812–821. doi: 10.1177/1947601910383418
  • Wang L, Liang C, Li F, et al. PARP1 in carcinomas and PARP1 inhibitors as antineoplastic drugs. Int J Mol Sci. 2017;18(10):2111. doi: 10.3390/ijms18102111
  • Salvati E, Scarsella M, Porru M, et al. PARP1 is activated at telomeres upon G4 stabilization: possible target for telomere-based therapy. Oncogene. 2010;29(47):6280–6293. doi: 10.1038/onc.2010.344
  • Zimmer J, Tacconi EMC, Folio C, et al. Targeting BRCA1 and BRCA2 deficiencies with G-Quadruplex-interacting compounds. Mol Cell. 2016;61(3):449–460. doi: 10.1016/j.molcel.2015.12.004
  • Xu H, Di Antonio M, McKinney S, et al. CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours. Nat Commun. 2017;8(1):14432. doi: 10.1038/ncomms14432
  • Salvati E, Botta L, Amato J, et al. Lead discovery of dual G-Quadruplex stabilizers and poly(ADP-ribose) polymerases (PARPs) inhibitors: a new avenue in anticancer treatment. J Med Chem. 2017;60(9):3626–3635. doi: 10.1021/acs.jmedchem.6b01563
  • Sengar A, Vandana JJ, Chambers VS, et al. Structure of a (3+1) hybrid G-quadruplex in the PARP1 promoter. Nucleic Acids Res. 2019;47(3):1564–1572. doi: 10.1093/nar/gky1179
  • Dallavalle S, Princiotto S, Mattio LM, et al. Investigation of the complexes formed between PARP1 inhibitors and PARP1 G-Quadruplex at the gene promoter region. Int J Mol Sci. 2021;22(16):8737. doi: 10.3390/ijms22168737
  • Dallavalle S, Musso L, Artali R, et al. G-quadruplex binding properties of a potent PARP-1 inhibitor derived from 7-azaindole-1-carboxamide. Sci Rep. 2021;11(1):3869. doi: 10.1038/s41598-021-83474-9
  • Masoud GN, Li W. HIF-1α pathway: role, regulation and intervention for cancer therapy. Acta Pharm Sin B. 2015;5(5):378–389. doi: 10.1016/j.apsb.2015.05.007
  • Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003;3(10):721–732. doi: 10.1038/nrc1187
  • Bárdos JI, Ashcroft M. Negative and positive regulation of HIF-1: a complex network. Biochim Biophys Acta - Rev Cancer. 2005;1755(2):107–120. doi: 10.1016/j.bbcan.2005.05.001
  • Semenza GL, Nejfelt MK, Chi SM, et al. Hypoxia-inducible nuclear factors bind to an enhancer element located 3’ to the human erythropoietin gene. Proc Natl Acad Sci. 1991;88(13):5680–5684. doi: 10.1073/pnas.88.13.5680
  • Heikkilä M, Pasanen A, Kivirikko KI, et al. Roles of the human hypoxia-inducible factor (HIF)-3α variants in the hypoxia response. Cell Mol Life Sci. 2011;68(23):3885–3901. doi: 10.1007/s00018-011-0679-5
  • Liberti MV, Locasale JW. The warburg effect: how does it benefit cancer cells? Trends Biochem Sci. 2016;41(3):211–218. doi: 10.1016/j.tibs.2015.12.001
  • Conway EM, Collen D, Carmeliet P. Molecular mechanisms of blood vessel growth. Cardiovasc Res. 2001;49(3):507–521. doi: 10.1016/S0008-6363(00)00281-9
  • De Armond R, Wood S, Sun D, et al. Evidence for the presence of a guanine quadruplex forming region within a polypurine tract of the hypoxia inducible factor 1α promoter. Biochemistry. 2005;44(49):16341–16350. doi: 10.1021/bi051618u
  • Lombardo CM, Welsh SJ, Strauss SJ, et al. A novel series of G-quadruplex ligands with selectivity for HIF-expressing osteosarcoma and renal cancer cell lines. Bioorg Med Chem Lett. 2012;22(18):5984–5988. doi: 10.1016/j.bmcl.2012.07.009
  • Welsh SJ, Dale AG, Lombardo CM, et al. Inhibition of the hypoxia-inducible factor pathway by a G-quadruplex binding small molecule. Sci Rep. 2013;3(1):2799. doi: 10.1038/srep02799
  • Chen H, Long H, Cui X, et al. Exploring the formation and recognition of an important G-Quadruplex in a HIF1α promoter and its transcriptional inhibition by a benzo[c]phenanthridine derivative. J Am Chem Soc. 2014;136(6):2583–2591. doi: 10.1021/ja412128w
  • Wen L, Han Z, Li J, et al. C-MYC and HIF1α promoter G-quadruplexes dependent metabolic regulation mechanism of berberine in colon cancer. J Gastrointest Oncol. 2022;13(3):1152–1168. doi: 10.21037/jgo-22-389
  • Takahashi M, Buma Y, Iwamoto T, et al. Cloning and expression of the ret proto-oncogene encoding a tyrosine kinase with two potential transmembrane domains. Oncogene. 1988;3(5):571–578.
  • Boulay A, Breuleux M, Stephan C, et al. The Ret receptor tyrosine kinase pathway functionally interacts with the ERα pathway in breast cancer. Cancer Res. 2008;68(10):3743–3751. doi: 10.1158/0008-5472.CAN-07-5100
  • Morandi A, Martin L-A, Gao Q, et al. GDNF–RET signaling in ER-Positive breast cancers is a key determinant of response and resistance to aromatase inhibitors. Cancer Res. 2013;73(12):3783–3795. doi: 10.1158/0008-5472.CAN-12-4265
  • Alqahtani T, Alswied A, Sun D. Selective antitumor activity of datelliptium toward medullary thyroid carcinoma by downregulating RET transcriptional activity. Cancers (Basel). 2021;13(13):3288. doi: 10.3390/cancers13133288
  • Gattelli A, Nalvarte I, Boulay A, et al. Ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells. EMBO Mol Med. 2013;5(9):1335–1350. doi: 10.1002/emmm.201302625
  • Andrew SD, Delhanty PJD, Mulligan LM, et al. Sp1 and Sp3 transactivate the RET proto-oncogene promoter. Gene. 2000;256(1–2):283–291. doi: 10.1016/S0378-1119(00)00302-4
  • Guo K, Pourpak A, Beetz-Rogers K, et al. Formation of pseudosymmetrical G-quadruplex and i-motif structures in the proximal promoter region of the RET oncogene. J Am Chem Soc. 2007;129(33):10220–10228. doi: 10.1021/ja072185g
  • Tong X, Lan W, Zhang X, et al. Solution structure of all parallel G-quadruplex formed by the oncogene RET promoter sequence. Nucleic Acids Res. 2011;39(15):6753–6763. doi: 10.1093/nar/gkr233
  • Wang F, Wang C, Liu Y, et al. Colchicine selective interaction with oncogene RET G-quadruplex revealed by NMR. Chem Commun. 2020;56(14):2099–2102. doi: 10.1039/D0CC00221F
  • Wang F, Wang C, Liu Y, et al. NMR studies on the interaction between oncogene RET G-quadruplex and berberine †. Chin J Chem. 2020;38(12):1656–1662. doi: 10.1002/cjoc.202000301
  • Kumarasamy VM, Shin Y-J, White J, et al. Selective repression of RET proto-oncogene in medullary thyroid carcinoma by a natural alkaloid berberine. BMC Cancer. 2015;15(1):599. doi: 10.1186/s12885-015-1610-5
  • Kumarasamy VM, Sun D. Demonstration of a potent RET transcriptional inhibitor for the treatment of medullary thyroid carcinoma based on an ellipticine derivative. Int J Oncol. 2017;51(1):145–157. doi: 10.3892/ijo.2017.3994
  • Lopergolo A, Perrone R, Tortoreto M, et al. Targeting of RET oncogene by naphthalene diimide-mediated gene promoter G-quadruplex stabilization exerts anti-tumor activity in oncogene-addicted human medullary thyroid cancer. Oncotarget. 2016;7(31):49649–49663. doi: 10.18632/oncotarget.10105
  • Oh I-H, Reddy EP. The myb gene family in cell growth, differentiation and apoptosis. Oncogene. 1999;18(19):3017–3033. doi: 10.1038/sj.onc.1202839
  • Todokoro K, Watson RJ, Higo H, et al. Down-regulation of c-myb gene expression is a prerequisite for erythropoietin-induced erythroid differentiation. Proc Natl Acad Sci. 1988;85(23):8900–8904. doi: 10.1073/pnas.85.23.8900
  • Yi HK, Nam SY, Kim JC, et al. Induction of apoptosis in K562 cells by dominant negative c-myb. Exp Hematol. 2002;30(10):1139–1146. doi: 10.1016/S0301-472X(02)00896-2
  • Gonda TJ, Metcalf D. Expression of myb, myc and fos proto-oncogenes during the differentiation of a murine myeloid leukaemia. Nature. 1984;310(5974):249–251. doi: 10.1038/310249a0
  • Fang F, Rycyzyn MA, Clevenger CV. Role of c-Myb during prolactin-induced signal transducer and activator of transcription 5a signaling in breast cancer cells. Endocrinology. 2009;150(4):1597–1606. doi: 10.1210/en.2008-1079
  • Matsugami A, Okuizumi T, Uesugi S, et al. Intramolecular higher order packing of parallel quadruplexes comprising a G: G: G: G tetrad and a G(: A): G(: A): G(: A): G heptad of GGA triplet repeat DNA. J Biol Chem. 2003;278(30):28147–28153. doi: 10.1074/jbc.M303694200
  • Palumbo SL, Memmott RM, Uribe DJ, et al. A novel G-quadruplex-forming GGA repeat region in the c-myb promoter is a critical regulator of promoter activity. Nucleic Acids Res. 2008;36(6):1755–1769. doi: 10.1093/nar/gkm1069
  • Cui X, Zhang Q, Chen H, et al. ESI Mass spectrometric exploration of selective recognition of G-Quadruplex in c - myb oncogene promoter using a novel flexible cyclic polyamide. J Am Soc Mass Spectrom. 2014;25(4):684–691. doi: 10.1007/s13361-013-0802-y
  • Liu Q, Wang Q, Lv C, et al. Brucine inhibits proliferation of glioblastoma cells by targeting the G-quadruplexes in the c-Myb promoter. J Cancer. 2021;12(7):1990–1999. doi: 10.7150/jca.53689
  • Neidle S. Quadruplex nucleic acids as novel therapeutic targets. J Med Chem. 2016;59(13):5987–6011. doi: 10.1021/acs.jmedchem.5b01835
  • Sengupta P, Bose D, Chatterjee S. The molecular Tête‐à‐Tête between G‐quadruplexes and the i‐motif in the human genome. Chembiochem. 2021;22(9):1517–1537. doi: 10.1002/cbic.202000703
  • Brooks TA, Hurley LH. Targeting MYC expression through G-Quadruplexes. Genes Cancer. 2010;1(6):641–649. doi: 10.1177/1947601910377493
  • Drygin D, Siddiqui-Jain A, O’Brien S, et al. Anticancer activity of CX-3543: a direct inhibitor of rRNA biogenesis. Cancer Res. 2009;69(19):7653–7661. doi: 10.1158/0008-5472.CAN-09-1304
  • Bruno PM, Lu M, Dennis KA, et al. The primary mechanism of cytotoxicity of the chemotherapeutic agent CX-5461 is topoisomerase II poisoning. Proc Natl Acad Sci. 2020;117(8):4053–4060. doi: 10.1073/pnas.1921649117
  • Hilton J, Gelmon K, Bedard PL, et al. Results of the phase I CCTG IND.231 trial of CX-5461 in patients with advanced solid tumors enriched for DNA-repair deficiencies. Nat Commun. 2022;13(1):3607. doi: 10.1038/s41467-022-31199-2
  • Pelliccia S, Amato J, Capasso D, et al. Bio-inspired dual-selective BCL-2/c-MYC G-Quadruplex binders: design, synthesis, and anticancer activity of drug-like Imidazo[2,1- i]purine derivatives. J Med Chem. 2020;63(5):2035–2050. doi: 10.1021/acs.jmedchem.9b00262
  • Nadai M, Cimino-Reale G, Sattin G, et al. Assessment of gene promoter G-quadruplex binding and modulation by a naphthalene diimide derivative in tumor cells. Int J Oncol. 2015;46(1):369–380. doi: 10.3892/ijo.2014.2723
  • Marchetti C, Zyner KG, Ohnmacht SA, et al. Targeting multiple effector pathways in pancreatic ductal adenocarcinoma with a G-quadruplex-binding small molecule. J Med Chem. 2018;61(6):2500–2517. doi: 10.1021/acs.jmedchem.7b01781
  • Ahmed A A. Asymmetrically Substituted Quadruplex-Binding Naphthalene Diimide Showing Potent Activity in Pancreatic Cancer Models. ACS Med Chem Lett. 2020;11(8):1634–1644. doi: 10.1021/acsmedchemlett.0c00317

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