3,406
Views
4
CrossRef citations to date
0
Altmetric
Review

The impact of RNA binding proteins and the associated long non-coding RNAs in the TCA cycle on cancer pathogenesis

ORCID Icon, , , &
Pages 223-234 | Accepted 16 May 2023, Published online: 23 May 2023

References

  • Faubert B, Solmonson A, DeBerardinis RJ. Metabolic reprogramming and cancer progression. Science. 2020;368. DOI:10.1126/science.aaw5473
  • Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–674.
  • Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov. 2022;12:31–46.
  • Warburg O, Wind F, Negelein E. The metabolism of tumors in the body. J Gen Physiol. 1927;8:519–530.
  • Gillies RJ, Gatenby RA. Adaptive landscapes and emergent phenotypes: why do cancers have high glycolysis? J Bioenerg Biomembr. 2007;39:251–257.
  • Pavlova NN, Thompson CB. The emerging hallmarks of cancer metabolism. Cell Metab. 2016;23:27–47.
  • Som P, Atkins HL, Bandoypadhyay D, et al. A fluorinated glucose analog, 2-fluoro-2-deoxy-D-glucose (F-18): nontoxic tracer for rapid tumor detection. J Nucl Med. 1980;21:670–675.
  • Papathanassiou D, Bruna-Muraille C, Jouannaud C, et al. Single-photon emission computed tomography combined with computed tomography (SPECT/CT) in bone diseases. Joint Bone Spine. 2009;76:474–480.
  • Sajnani K, Islam F, Smith RA, et al. Genetic alterations in Krebs cycle and its impact on cancer pathogenesis. Biochimie. 2017;135:164–172.
  • Chen JQ, Russo J. Dysregulation of glucose transport, glycolysis, TCA cycle and glutaminolysis by oncogenes and tumor suppressors in cancer cells. Biochim Biophys Acta. 2012;1826:370–384.
  • Eniafe J, Jiang S. The functional roles of TCA cycle metabolites in cancer. Oncogene. 2021;40:3351–3363.
  • Hung CL, Wang LY, Yu YL, et al. A long noncoding RNA connects c-Myc to tumor metabolism. Proc Natl Acad Sci U S A. 2014;111:18697–18702.
  • Park MK, Zhang L, Min KW, et al. (2021) NEAT1 is essential for metabolic changes that promote breast cancer growth and metastasis. Cell Metab, 33, 2380–2397 e2389.
  • Sang L, Ju HQ, Yang Z, et al. Mitochondrial long non-coding RNA GAS5 tunes TCA metabolism in response to nutrient stress. Nat Metab. 2021;3:90–106.
  • Zhang X, Li Z, Xuan Z, et al. Novel role of miR-133a-3p in repressing gastric cancer growth and metastasis via blocking autophagy-mediated glutaminolysis. J Exp Clin Cancer Res. 2018;37:320.
  • Eng C, Kiuru M, Fernandez MJ, et al. A role for mitochondrial enzymes in inherited neoplasia and beyond. Nat Rev Cancer. 2003;3:193–202.
  • Juang HH. Modulation of mitochondrial aconitase on the bioenergy of human prostate carcinoma cells. Mol Genet Metab. 2004;81:244–252.
  • Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009;360:765–773.
  • Tian C, Wen B, Bian M, et al. From a dimer to a monomer: construction of a chimeric monomeric isocitrate dehydrogenase. Protein Sci. 2021;30:2396–2407.
  • Zheng ZQ, Li ZX, Guan JL, et al. Long noncoding RNA TINCR-Mediated regulation of acetyl-CoA metabolism promotes nasopharyngeal carcinoma progression and chemoresistance. Cancer Res. 2020;80:5174–5188.
  • Qin H, Ni H, Liu Y, et al. RNA-binding proteins in tumor progression. J Hematol Oncol. 2020;13:90.
  • Li L, Miao H, Chang Y, et al. Multidimensional crosstalk between RNA-binding proteins and noncoding RNAs in cancer biology. Semin Cancer Biol. 2021;75:84–96.
  • Mattick JS, Amaral PP, Carninci P, et al. Long non-coding RNAs: definitions, functions, challenges and recommendations. Nat Rev Mol Cell Biol. 2023. doi:10.1038/s41580-022-00566-8.
  • Tan YT, Lin JF, Li T, et al. LncRNA-mediated posttranslational modifications and reprogramming of energy metabolism in cancer. Cancer Commun (Lond). 2021;41:109–120.
  • Xiang S, Gu H, Jin L, et al. LncRNA IDH1-AS1 links the functions of c-Myc and HIF1alpha via IDH1 to regulate the Warburg effect. Proc Natl Acad Sci U S A. 2018;115:E1465–1474.
  • Mullen AR, DeBerardinis RJ. Genetically-defined metabolic reprogramming in cancer. Trends Endocrinol Metab. 2012;23:552–559.
  • Migita T, Narita T, Nomura K, et al. ATP citrate lyase: activation and therapeutic implications in non-small cell lung cancer. Cancer Res. 2008;68:8547–8554.
  • Corbet C, Feron O. Cancer cell metabolism and mitochondria: nutrient plasticity for TCA cycle fueling. Biochim Biophys Acta Rev Cancer. 2017;1868:7–15.
  • Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nat Rev Cancer. 2004;4:891–899.
  • Kim JW, Tchernyshyov I, Semenza GL, et al. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006;3:177–185.
  • Gao C, Shen Y, Jin F, et al. Cancer stem cells in small cell lung cancer cell line H446: higher dependency on oxidative phosphorylation and mitochondrial substrate-level phosphorylation than non-stem cancer cells. PLoS ONE. 2016;11:e0154576.
  • Kishton RJ, Barnes CE, Nichols AG, et al. AMPK is essential to balance glycolysis and mitochondrial metabolism to control T-ALL cell stress and survival. Cell Metab. 2016;23:649–662.
  • Schito L, Semenza GL. Hypoxia-inducible factors: master regulators of cancer progression. Trends Cancer. 2016;2:758–770.
  • Shen T, Xia W, Min S, et al. A pair of long intergenic non-coding RNA LINC00887 variants act antagonistically to control Carbonic Anhydrase IX transcription upon hypoxia in tongue squamous carcinoma progression. BMC Biol. 2021;19:192.
  • Gameiro PA, Yang J, Metelo AM, et al. In vivo HIF-mediated reductive carboxylation is regulated by citrate levels and sensitizes VHL-deficient cells to glutamine deprivation. Cell Metab. 2013;17:372–385.
  • Le A, Lane AN, Hamaker M, et al. Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells. Cell Metab. 2012;15:110–121.
  • Gaude E, Frezza C. Defects in mitochondrial metabolism and cancer. Cancer Metab. 2014;2:10.
  • Cardaci S, Ciriolo MR. TCA cycle defects and cancer: when metabolism tunes redox state. Int J Cell Biol. 2012;2012:161837.
  • Yang M, Soga T, Pollard PJ. Oncometabolites: linking altered metabolism with cancer. J Clin Invest. 2013;123:3652–3658.
  • Desideri E, Vegliante R, Ciriolo MR. Mitochondrial dysfunctions in cancer: genetic defects and oncogenic signaling impinging on TCA cycle activity. Cancer Lett. 2015;356:217–223.
  • Isaacs JS, Jung YJ, Mole DR, et al. HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability. Cancer Cell. 2005;8:143–153.
  • Selak MA, Armour SM, MacKenzie ED, et al. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell. 2005;7:77–85.
  • DeNicola GM, Karreth FA, Humpton TJ, et al. Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature. 2011;475:106–109.
  • Saito R, Suzuki T, Hiramoto K, et al. Characterizations of three major cysteine sensors of keap1 in stress response. Mol Cell Biol. 2016;36:271–284.
  • Moreno Leon L, Gautier M, Allan R, et al. The nuclear hypoxia-regulated NLUCAT1 long non-coding RNA contributes to an aggressive phenotype in lung adenocarcinoma through regulation of oxidative stress. Oncogene. 2019;38:7146–7165.
  • Liang D, Kong X, Sang N. Effects of histone deacetylase inhibitors on HIF-1. Cell Cycle. 2006;5:2430–2435.
  • Kacso TP, Zahu R, Tirpe A, et al. Reactive oxygen species and long non-coding RNAs, an unexpected crossroad in cancer cells. Int J Mol Sci. 2022;23:10133.
  • Chen F, Xiao M, Feng J, et al. Different inhibition of Nrf2 by two keap1 isoforms alpha and beta to shape malignant behaviour of human hepatocellular carcinoma. Int J Mol Sci. 2022;23:10342.
  • Zhao H, He Y, Li H, et al. The opposite role of alternatively spliced isoforms of LINC00477 in gastric cancer. Cancer Manag Res. 2019;11:4569–4576.
  • Xu F, Hua Q, Zhang A, et al. LncRNA AC020978 facilitates non-small cell lung cancer progression by interacting with malate dehydrogenase 2 and activating the AKT pathway. Cancer Sci. 2021;112:4501–4514.
  • Yang J, Liu F, Wang Y, et al. LncRNAs in tumor metabolic reprogramming and immune microenvironment remodeling. Cancer Lett. 2022;543:215798.
  • Ferre F, Colantoni A, Helmer-Citterich M. Revealing protein-lncRNA interaction. Brief Bioinform. 2016;17:106–116.
  • Pereira B, Billaud M, Almeida R. RNA-Binding proteins in cancer: old players and new actors. Trends Cancer. 2017;3:506–528.
  • Lunde BM, Moore C, Varani G. RNA-binding proteins: modular design for efficient function. Nat Rev Mol Cell Biol. 2007;8:479–490.
  • Albihlal WS, Gerber AP. Unconventional RNA-binding proteins: an uncharted zone in RNA biology. FEBS Lett. 2018;592:2917–2931.
  • Castello A, Fischer B, Eichelbaum K, et al. Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell. 2012;149:1393–1406.
  • Castello A, Hentze MW, Preiss T. Metabolic enzymes enjoying new partnerships as RNA-Binding proteins. Trends Endocrinol Metab. 2015;26:746–757.
  • Ciesla J. Metabolic enzymes that bind RNA: yet another level of cellular regulatory network? Acta Biochim Pol. 2006;53:11–32.
  • Zaidi N, Swinnen JV, Smans K. ATP-citrate lyase: a key player in cancer metabolism. Cancer Res. 2012;72:3709–3714.
  • Icard P, Wu Z, Alifano M, et al. Gluconeogenesis of cancer cells is disrupted by citrate. Trends Cancer. 2019;5:265–266.
  • Wang J, Ye W, Yan X, et al. Low expression of ACLY associates with favorable prognosis in acute myeloid leukemia. J Transl Med. 2019;17:149.
  • Elshourbagy NA, Near JC, Kmetz PJ, et al. Cloning and expression of a human ATP-citrate lyase cDNA. Eur J Biochem. 1992;204:491–499.
  • Zhang G, Wang Q, Lu J, et al. Long non-coding RNA FLJ22763 is involved in the progression and prognosis of gastric cancer. Gene. 2019;693:84–91.
  • Volz K. The functional duality of iron regulatory protein 1. Curr Opin Struct Biol. 2008;18:106–111.
  • Yuan C, Clish CB, Wu C, et al. Circulating metabolites and survival among patients with pancreatic cancer. J Natl Cancer Inst. 2016;108:djv409.
  • Zhang T, Sun L, Hao Y, et al. ENO1 suppresses cancer cell ferroptosis by degrading the mRNA of iron regulatory protein 1. Nat Cancer. 2022;3:75–89.
  • Dang L, Yen K, Attar EC. IDH mutations in cancer and progress toward development of targeted therapeutics. Ann Oncol. 2016;27:599–608.
  • Pirozzi CJ, Yan H. The implications of IDH mutations for cancer development and therapy. Nat Rev Clin Oncol. 2021;18:645–661.
  • Caravella JA, Lin J, Diebold RB, et al. Structure-based design and identification of FT-2102 (Olutasidenib), a potent mutant-selective IDH1 inhibitor. J Med Chem. 2020;63:1612–1623.
  • Wang J, Quan Y, Lv J, et al. LncRNA IDH1-AS1 suppresses cell proliferation and tumor growth in glioma. Biochem Cell Biol. 2020;98:556–564.
  • Ait-El-Mkadem S, Dayem-Quere M, Gusic M, et al. Mutations in MDH2, encoding a Krebs cycle enzyme, cause early-onset severe encephalopathy. Am J Hum Genet. 2017;100:151–159.
  • Marquez J, Flores J, Kim AH, et al. Rescue of TCA cycle dysfunction for cancer therapy. J Clin Med. 2019;8:2161.
  • Lo YW, Lin ST, Chang SJ, et al. Mitochondrial proteomics with siRNA knockdown to reveal ACAT1 and MDH2 in the development of doxorubicin-resistant uterine cancer. J Cell Mol Med. 2015;19:744–759.
  • Liu Q, Harvey CT, Geng H, et al. Malate dehydrogenase 2 confers docetaxel resistance via regulations of JNK signaling and oxidative metabolism. Prostate. 2013;73:1028–1037.
  • Bao X, Guo X, Yin M, et al. Capturing the interactome of newly transcribed RNA. Nat Methods. 2018;15:213–220.
  • Castello A, Fischer B, Frese CK, et al. Comprehensive identification of RNA-Binding domains in human cells. Mol Cell. 2016;63:696–710.
  • Conrad T, Albrecht AS, de Melo Costa VR, et al. Serial interactome capture of the human cell nucleus. Nat Commun. 2016;7:11212.
  • Guo X, Tariq M, Lai Y, et al. Capture of the newly transcribed RNA interactome using click chemistry. Nat Protoc. 2021;16:5193–5219.
  • He C, Sidoli S, Warneford-Thomson R, et al. High-resolution mapping of RNA-binding regions in the nuclear proteome of embryonic stem cells. Mol Cell. 2016;64:416–430.
  • Huang R, Han M, Meng L, et al. Transcriptome-wide discovery of coding and noncoding RNA-binding proteins. Proc Natl Acad Sci U S A. 2018;115:E3879–3887.
  • Li X, Song J, Yi C. Genome-wide mapping of cellular protein-RNA interactions enabled by chemical crosslinking. Genomics Proteomics Bioinf. 2014;12:72–78.
  • Queiroz RML, Smith T, Villanueva E, et al. Comprehensive identification of RNA-protein interactions in any organism using orthogonal organic phase separation (OOPS). Nat Biotechnol. 2019;37:169–178.
  • Trendel J, Schwarzl T, Horos R, et al. The human RNA-Binding proteome and its dynamics during translational arrest. Cell. 2019;176:391–403 e319.
  • Yan S, Zhao D, Wang C, et al. Characterization of RNA-binding proteins in the cell nucleus and cytoplasm. Anal Chim Acta. 2021;1168:338609.
  • Caudron-Herger M, Wassmer E, Nasa I, et al. Identification, quantification and bioinformatic analysis of RNA-dependent proteins by RNase treatment and density gradient ultracentrifugation using R-DeeP. Nat Protoc. 2020;15:1338–1370.
  • Brannan KW, Jin W, Huelga SC, et al. SONAR discovers RNA-Binding proteins from analysis of large-scale protein-protein interactomes. Mol Cell. 2016;64:282–293.
  • Kang J, Tang Q, He J, et al. Rnainter v4.0: rNA interactome repository with redefined confidence scoring system and improved accessibility. Nucleic Acids Res. 2022;50:D326–332.
  • Li JH, Liu S, Zhou H, et al. starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 2014;42:D92–97.
  • Teng X, Chen X, Xue H, et al. Npinter v4.0: an integrated database of ncRNA interactions. Nucleic Acids Res. 2020;48:D160–165.
  • Zhang J, Chen Q, Liu B. iDRBP_MMC: identifying DNA-Binding proteins and RNA-binding proteins based on multi-label learning model and motif-based convolutional neural network. J Mol Biol. 2020;432:5860–5875.
  • Suresh V, Liu L, Adjeroh D, et al. RPI-Pred: predicting ncRNA-protein interaction using sequence and structural information. Nucleic Acids Res. 2015;43:1370–1379.
  • Livi CM, Klus P, Delli Ponti R, et al. catRAPID signature: identification of ribonucleoproteins and RNA-binding regions. Bioinformatics. 2016;32:773–775.
  • Granchi C. ATP citrate lyase (ACLY) inhibitors: an anti-cancer strategy at the crossroads of glucose and lipid metabolism. Eur J Med Chem. 2018;157:1276–1291.
  • Huang D, Wang Y, Thompson JW, et al. Cancer-cell-derived GABA promotes beta-catenin-mediated tumour growth and immunosuppression. Nat Cell Biol. 2022;24:230–241.
  • Jansen MP, Sas L, Sieuwerts AM, et al. Decreased expression of ABAT and STC2 hallmarks ER-positive inflammatory breast cancer and endocrine therapy resistance in advanced disease. Mol Oncol. 2015;9:1218–1233.
  • Jin L, Chun J, Pan C, et al. The PLAG1-GDH1 axis promotes anoikis resistance and tumor metastasis through CamKK2-AMPK signaling in LKB1-deficient lung cancer. Mol Cell. 2018;69:87–99 e87.
  • Kremer JC, Prudner BC, Lange SES, et al. Arginine deprivation inhibits the Warburg effect and upregulates glutamine anaplerosis and serine biosynthesis in ASS1-deficient cancers. Cell Rep. 2017;18:991–1004.
  • Lao-On U, Rojvirat P, Chansongkrow P, et al. C-Myc directly targets an over-expression of pyruvate carboxylase in highly invasive breast cancer. Biochim Biophys Acta Mol Basis Dis. 2020;1866:165656.
  • Qi L, Martin-Sandoval MS, Merchant S, et al. Aspartate availability limits hematopoietic stem cell function during hematopoietic regeneration. Cell Stem Cell. 2021;28:1982–1999 e1988.
  • Sawant Dessai A, Dominguez MP, Chen UI, et al. Transcriptional repression of SIRT3 potentiates mitochondrial aconitase activation to drive aggressive prostate cancer to the bone. Cancer Res. 2021;81:50–63.
  • Tian X, Han Y, Yu L, et al. Decreased expression of ALDH5A1 predicts prognosis in patients with ovarian cancer. Cancer Biol Ther. 2017;18:245–251.
  • You X, Tian J, Zhang H, et al. Loss of mitochondrial aconitase promotes colorectal cancer progression via SCD1-mediated lipid remodeling. Mol Metab. 2021;48:101203.
  • Zheng B, Chai R, Yu X. Downregulation of NIT2 inhibits colon cancer cell proliferation and induces cell cycle arrest through the caspase-3 and PARP pathways. Int J Mol Med. 2015;35:1317–1322.
  • Zou Z, Hu X, Luo T, et al. Naturally-occurring spinosyn a and its derivatives function as argininosuccinate synthase activator and tumor inhibitor. Nat Commun. 2021;12:2263.
  • Ghiam AF, Cairns RA, Thoms J, et al. IDH mutation status in prostate cancer. Oncogene. 2012;31:3826.
  • Bardella C, Pollard PJ, Tomlinson I. SDH mutations in cancer. Biochim Biophys Acta. 2011;1807:1432–1443.
  • Tomlinson IP, Alam NA, Rowan AJ, et al. Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet. 2002;30:406–410.
  • Lin CC, Cheng TL, Tsai WH, et al. Loss of the respiratory enzyme citrate synthase directly links the Warburg effect to tumor malignancy. Sci Rep. 2012;2:785.
  • Chang LC, Chiang SK, Chen SE, et al. Targeting 2-oxoglutarate dehydrogenase for cancer treatment. Am J Cancer Res. 2022;12:1436–1455.
  • Dai W, Xu L, Yu X, et al. OGDHL silencing promotes hepatocellular carcinoma by reprogramming glutamine metabolism. J Hepatol. 2020;72:909–923.
  • Anderson NM, Qin X, Finan JM, et al. Metabolic enzyme DLST promotes tumor aggression and reveals a vulnerability to OXPHOS inhibition in high-risk neuroblastoma. Cancer Res. 2021;81:4417–4430.
  • Cascon A, Comino-Mendez I, Curras-Freixes M, et al. Whole-exome sequencing identifies MDH2 as a new familial paraganglioma gene. J Natl Cancer Inst. 2015;107. DOI:10.1093/jnci/djv053
  • Kang MR, Kim MS, Oh JE, et al. Mutational analysis of IDH1 codon 132 in glioblastomas and other common cancers. Int J Cancer. 2009;125:353–355.
  • Ohgaki H, Kleihues P. The definition of primary and secondary glioblastoma. Clin Cancer Res. 2013;19:764–772.
  • Yang M, Ternette N, Su H, et al. The succinated proteome of FH-mutant tumours. Metabolites. 2014;4:640–654.
  • Yen KE, Bittinger MA, Su SM, et al. Cancer-associated IDH mutations: biomarker and therapeutic opportunities. Oncogene. 2010;29:6409–6417.
  • Astuti D, Latif F, Dallol A, et al. Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. Am J Hum Genet. 2001;69:49–54.
  • Bayley JP, Kunst HP, Cascon A, et al. SDHAF2 mutations in familial and sporadic paraganglioma and phaeochromocytoma. Lancet Oncol. 2010;11:366–372.
  • Baysal BE, Willett-Brozick JE, Lawrence EC, et al. Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas. J Med Genet. 2002;39:178–183.
  • Burnichon N, Briere JJ, Libe R, et al. SDHA is a tumor suppressor gene causing paraganglioma. Hum Mol Genet. 2010;19:3011–3020.
  • Hao HX, Khalimonchuk O, Schraders M, et al. SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma. Science. 2009;325:1139–1142.
  • Niemann S, Muller U. Mutations in SDHC cause autosomal dominant paraganglioma, type 3. Nat Genet. 2000;26:268–270.
  • Moog S, Lussey-Lepoutre C, Favier J. Epigenetic and metabolic reprogramming of SDH-deficient paragangliomas. Endocr Relat Cancer. 2020;27:R451–463.
  • Buelow B, Cohen J, Nagymanyoki Z, et al. Immunohistochemistry for 2-Succinocysteine (2SC) and Fumarate Hydratase (FH) in cutaneous leiomyomas may aid in identification of patients with HLRCC (Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome). Am J Surg Pathol. 2016;40:982–988.
  • Kancherla P, Daneshvar M, Sager RA, et al. Fumarate hydratase as a therapeutic target in renal cancer. Expert Opin Ther Targets. 2020;24:923–936.
  • Launonen V, Vierimaa O, Kiuru M, et al. Inherited susceptibility to uterine leiomyomas and renal cell cancer. Proc Natl Acad Sci U S A. 2001;98:3387–3392.
  • Carvajal-Carmona LG, Alam NA, Pollard PJ, et al. Adult leydig cell tumors of the testis caused by germline fumarate hydratase mutations. J Clin Endocrinol Metab. 2006;91:3071–3075.
  • Ylisaukko-Oja SK, Cybulski C, Lehtonen R, et al. Germline fumarate hydratase mutations in patients with ovarian mucinous cystadenoma. Eur J Hum Genet. 2006;14:880–883.
  • Li S, Chou AP, Chen W, et al. Overexpression of isocitrate dehydrogenase mutant proteins renders glioma cells more sensitive to radiation. Neuro Oncol. 2013;15:57–68.
  • Chen L, Liu T, Zhou J, et al. Citrate synthase expression affects tumor phenotype and drug resistance in human ovarian carcinoma. PLoS ONE. 2014;9:e115708.
  • Schlichtholz B, Turyn J, Goyke E, et al. Enhanced citrate synthase activity in human pancreatic cancer. Pancreas. 2005;30:99–104.
  • Fedorova MS, Kudryavtseva AV, Lakunina VA, et al. Downregulation of OGDHL expression is associated with promoter hypermethylation in colorectal cancer. Mol Biol (Mosk). 2015;49:678–688.
  • Hoque MO, Kim MS, Ostrow KL, et al. Genome-wide promoter analysis uncovers portions of the cancer methylome. Cancer Res. 2008;68:2661–2670.
  • Ostrow KL, Park HL, Hoque MO, et al. Pharmacologic unmasking of epigenetically silenced genes in breast cancer. Clin Cancer Res. 2009;15:1184–1191.
  • Snezhkina AV, Krasnov GS, Zaretsky AR, et al. Differential expression of alternatively spliced transcripts related to energy metabolism in colorectal cancer. BMC Genomics. 2016;17:1011.
  • Anderson NM, Li D, Peng HL, et al. The TCA cycle transferase DLST is important for MYC-mediated leukemogenesis. Leukemia. 2016;30:1365–1374.
  • Shin D, Lee J, You JH, et al. Dihydrolipoamide dehydrogenase regulates cystine deprivation-induced ferroptosis in head and neck cancer. Redox Biol. 2020;30:101418.
  • Ciccarone F, Vegliante R, Di Leo L, et al. The TCA cycle as a bridge between oncometabolism and DNA transactions in cancer. Semin Cancer Biol. 2017;47:50–56.
  • Luo Y, Ma J, Lu W. The significance of mitochondrial dysfunction in cancer. Int J Mol Sci. 2020;21:5598.
  • Anderson NM, Mucka P, Kern JG, et al. The emerging role and targetability of the TCA cycle in cancer metabolism. Protein Cell. 2018;9:216–237.
  • Rohle D, Popovici-Muller J, Palaskas N, et al. An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science. 2013;340:626–630.
  • Wang F, Travins J, DeLabarre B, et al. Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation. Science. 2013;340:622–626.
  • Ilic N, Birsoy K, Aguirre AJ, et al. PIK3CA mutant tumors depend on oxoglutarate dehydrogenase. Proc Natl Acad Sci U S A. 2017;114:E3434–3443.
  • Stuart SD, Schauble A, Gupta S, et al. A strategically designed small molecule attacks alpha-ketoglutarate dehydrogenase in tumor cells through a redox process. Cancer Metab. 2014;2:4.
  • Zachar Z, Marecek J, Maturo C, et al. Non-redox-active lipoate derivates disrupt cancer cell mitochondrial metabolism and are potent anticancer agents in vivo. J Mol Med (Berl). 2011;89:1137–1148.
  • Neitzel C, Demuth P, Wittmann S, et al. Targeting altered energy metabolism in colorectal cancer: oncogenic reprogramming, the central role of the TCA cycle and therapeutic opportunities. Cancers (Basel). 2020;12(7):12.
  • Chandra Gupta S, Nandan Tripathi Y. Potential of long non-coding RNAs in cancer patients: from biomarkers to therapeutic targets. Int J Cancer. 2017;140:1955–1967.
  • Mizrahi A, Czerniak A, Levy T, et al. Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences. J Transl Med. 2009;7:69.
  • Sharma U, Barwal TS, Malhotra A, et al. Long non-coding RNA TINCR as potential biomarker and therapeutic target for cancer. Life Sci. 2020;257:118035.
  • Tian T, Wang M, Lin S, et al. The impact of lncRNA dysregulation on clinicopathology and survival of breast cancer: a systematic review and meta-analysis. Mol Ther Nucleic Acids. 2018;12:359–369.
  • Xia Y, Liu Z, Yu W, et al. The prognostic significance of long noncoding RNAs in bladder cancer: a meta-analysis. PLoS ONE. 2018;13:e0198602.
  • Ghaforui-Fard S, Taheri M. Growth arrest specific transcript 5 in tumorigenesis process: an update on the expression pattern and genomic variants. Biomed Pharmacother. 2019;112:108723.
  • Chen Y, Li Z, Chen X, et al. Long non-coding RNAs: from disease code to drug role. Acta Pharm Sin B. 2021;11:340–354.
  • Hong S. RNA binding protein as an emerging therapeutic target for cancer prevention and treatment. J Cancer Prev. 2017;22:203–210.
  • Cai Z, Li CF, Han F, et al. Phosphorylation of PDHA by AMPK drives TCA cycle to promote cancer metastasis. Mol Cell. 2020;80:263–278 e267.
  • Wang X, Song X, Glass CK, et al. The long arm of long noncoding RNAs: roles as sensors regulating gene transcriptional programs. Cold Spring Harb Perspect Biol. 2011;3:a003756.
  • Kishton RJ, Rathmell JC. Novel therapeutic targets of tumor metabolism. Cancer J. 2015;21:62–69.
  • Martinez-Outschoorn UE, Peiris-Pages M, Pestell RG, et al. Cancer metabolism: a therapeutic perspective. Nat Rev Clin Oncol. 2017;14:11–31.
  • Obre E, Rossignol R. Emerging concepts in bioenergetics and cancer research: metabolic flexibility, coupling, symbiosis, switch, oxidative tumors, metabolic remodeling, signaling and bioenergetic therapy. Int J Biochem Cell Biol. 2015;59:167–181.
  • Yuneva MO, Fan TW, Allen TD, et al. The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type. Cell Metab. 2012;15:157–170.
  • Zugazagoitia J, Guedes C, Ponce S, et al. Current challenges in cancer treatment. Clin Ther. 2016;38:1551–1566.