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Review

Pre-mRNA splicing in cancer: the relevance in oncogenesis, treatment and drug resistance

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Bibliography

  • SBerget, CMoore, PSharp. Spliced segments at the 5’ terminus of adenovirus 2 late mRNA. Proc Natl Acad Sci USA 1977;74:3171-5
  • LChow, RGelinas, TBroker, RRoberts. An amazing sequence arrangement at the 5’ ends of adenovirus 2 messenger RNA. Cell 1977;12:1-8
  • TWNilsen, BRGraveley. Expansion of the eukaryotic proteome by alternative splicing. Nature 2010;463:457-63
  • MChen, JManley. Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches. Nat Rev Mol Cell Biol 2009;10:741-54
  • MCWahl, CLWill, RLührmann. The spliceosome: design principles of a dynamic RNP machine. Cell 2009;136:701-18
  • DASterner, TCarlo, SMBerget. Architectural limits on split genes. Proc Natl Acad Sci USA 1996;93:15081-5
  • NAFaustino, TACooper. Pre-mRNA splicing and human disease. Genes Dev 2003;17:419-37
  • AGuttmacher. Genomic medicine—a primer. N Enlg J Med 2002;347:1512-20
  • CLWill, RLührmann. Spliceosome structure and function. Cold Spring Harb Perspect Biol 2011;3(7):a003707
  • AJMatlin, FClark, CWSmith. Understanding alternative splicing: towards a cellular code. Nat Rev Mol Cell Biol 2005;6:386-98
  • AJLopez. Alternative splicing of pre-mRNA: developmental consequences and mechanisms of regulation. Annu Rev Genet 1998;32:279-305
  • CGhigna, CValacca, GBiamonti. Alternative splicing and tumor progression. Curr Genomics 2008;9:556-70
  • XDFu, MAres. Context-dependent control of alternative splicing by RNA-binding proteins. Nat Rev Genet 2014;15:689-701
  • JTWitten, JUle. Understanding splicing regulation through RNA splicing maps. Trends Genet 2011;27:89-97
  • QLi, J-ALee, DLBlack. Neuronal regulation of alternative pre-mRNA splicing. Nat Rev Neurosci 2007;8:819-31
  • LCartegni, SLChew, ARKrainer. Listening To Silence and Understanding Nonsense: exonic Mutations That Affect Splicing. Nat Rev Genet 2002;3:285-98
  • DMBhatt, APandya-Jones, AJTong, et al. Transcript dynamics of proinflammatory genes revealed by sequence analysis of subcellular RNA fractions. Cell 2012;150:279-90
  • HTilgner, DGKnowles, RJohnson, et al. Deep sequencing of subcellular RNA fractions shows splicing to be predominantly co-transcriptional in the human genome but inefficient for lncRNAs. Genome Res 2012;22:1616-25
  • FCarrillo Oesterreich, SPreibisch, KMNeugebauer. Global analysis of nascent RNA reveals transcriptional pausing in terminal exons. Mol Cell 2010;40:571-81
  • ERosonina, BJBlencowe. Gene expression: the close coupling of transcription and splicing. Curr Biol 2002;12(9):R319-21
  • CJDavid, ARBoyne, SRMillhouse, JLManley. The RNA polymerase II C-terminal domain promotes splicing activation through recruitment of a U2AF65-Prp19 complex. Genes Dev 2011;25:972-83
  • FCarrillo Oesterreich, NBieberstein, KMNeugebauer. Pause locally, splice globally. Trends Cell Biol 2011;21:328-35
  • GSWang, TACooper. Splicing in disease: disruption of the splicing code and the decoding machinery. Nat Rev Genet 2007;8:749-61
  • DKaida, TSchneider-Poetsch, MYoshida. Splicing in oncogenesis and tumor suppression. Cancer Sci 2012;103:1611-16
  • SBonomi, SGallo, MCatillo, et al. Oncogenic alternative splicing switches: role in cancer progression and prospects for therapy. Int J Cell Biol 2013;2013:962038
  • ASrebrow, ARKornblihtt. The connection between splicing and cancer. J Cell Sci 2006;119:2635-41
  • LLChen, MSabripour, EFWu, et al. A mutation-created novel intra-exonic pre-mRNA splice site causes constitutive activation of KIT in human gastrointestinal stromal tumors. Oncogene 2005;24:4271-80
  • MPKhoury, JCBourdon. The isoforms of the p53 protein. Cold Spring Harb Perspect Biol 2010;2:a000927
  • SDas, ARKrainer. Emerging functions of SRSF1, splicing factor and oncoprotein, in RNA metabolism and cancer. Mol Cancer Res 2014;12:1195-204
  • RKarni, Ede Stanchina, SWLowe, et al. The gene encoding the splicing factor SF2/ASF is a proto-oncogene. Nat Struct Mol Biol 2007;14:185-93
  • OAnczuków, AZRosenberg, MAkerman, et al. The splicing factor SRSF1 regulates apoptosis and proliferation to promote mammary epithelial cell transformation. Nat Struct Mol Biol 2012;19:220-8
  • ARGrosso, SMartins, MCarmo-Fonseca. The emerging role of splicing factors in cancer. EMBO Rep 2008;9:1087-93
  • BMBrinkman. Splice variants as cancer biomarkers. Clin Biochem 2004;37:584-94
  • WJin, IMcCutcheon, GFuller, et al. Fibroblast growth factor receptor-1 α-exon exclusion and polypyrimidine tract-binding protein in glioblastoma multiforme tumors. Cancer Res 2000;60:1221-4
  • YWang, DChen, HQian, et al. The Splicing Factor RBM4 Controls Apoptosis, Proliferation, and Migration to Suppress Tumor Progression. Cancer Cell 2014;26:374-89
  • SAdamia, BHaibe-Kains. A genome-wide aberrant RNA splicing in patients with acute myeloid leukemia identifies novel potential disease markers and therapeutic targets. Clin Cancer Res 2014;20:1135-45
  • FDamm, FNguyen-Khac, MFontenay, OABernard. Spliceosome and other novel mutations in chronic lymphocytic leukemia and myeloid malignancies. Leukemia 2012;26:2027-31
  • FDamm, OKosmider, VGelsi-Boyer, et al. Mutations affecting mRNA splicing define distinct clinical phenotypes and correlate with patient outcome in myelodysplastic syndromes. Blood 2012;119:3211-18
  • DRossi, ABruscaggin, VSpina, et al. Mutations of the SF3B1 splicing factor in chronic lymphocytic leukemia: association with progression and fludarabine-refractoriness. Blood 2011;118:6904-8
  • EPapaemmanuil, MGerstung, LMalcovati, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood 2013;122:3616-27
  • VVisconte, HMakishima, JPMaciejewski, VTiu R. Emerging roles of the spliceosomal machinery in myelodysplastic syndromes and other hematological disorders. Leukemia 2012;26:2447-54
  • LMalcovati, EPapaemmanuil, DTBowen, et al. Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms. Blood 2011;118:6239-46
  • FThol, SKade, CSchlarmann, et al. Frequency and prognostic impact of mutations in SRSF2, U2AF1, and ZRSR2 in patients with myelodysplastic syndromes. Blood 2012;119:3578-84
  • TAGraubert, DShen, LDing, et al. Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes. Nat Genet 2012;44:53-7
  • AKurtovic-Kozaric, BPrzychodzen, JSingh, et al. PRPF8 defects cause missplicing in myeloid malignancies. Leukemia 2014. [ Epub ahead of print]
  • KYoshida, MSanada, YShiraishi, et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 2011;478:64-9
  • SAKar, AJankowska, HMakishima, et al. Spliceosomal gene mutations are frequent events in the diverse mutational spectrum of chronic myelomonocytic leukemia but largely absent in juvenile myelomonocytic leukemia. Haematologica 2013;98:107-13
  • RItzykson, OKosmider, ARenneville, et al. Prognostic score including gene mutations in chronic myelomonocytic leukemia. J Clin Oncol 2013;31:2428-36
  • MMPatnaik, TLLasho, CMFinke, et al. Spliceosome mutations involving SRSF2, SF3B1, and U2AF35 in chronic myelomonocytic leukemia: prevalence, clinical correlates, and prognostic relevance. Am J Hematol 2013;88:201-6
  • MMeggendorfer, ARoller, THaferlach, et al. SRSF2 mutations in 275 cases with chronic myelomonocytic leukemia (CMML). Blood 2012;120:3080-8
  • SMDehm. mRNA splicing variants: exploiting modularity to outwit cancer therapy. Cancer Res 2013;73:5309-14
  • AWojtuszkiewicz, GJSchuurhuis, FLKessler, et al. Transfer of regulatory protein networks via extracellular vesicles as a candidate mechanism of apoptosis-resistance in acute myeloid leukemia [abstract]. Proc 105th AACR Annu Meet Am Assoc Cancer Res 2014; San Diego, CA Philadelphia; 5 – 9Apr 2014; Abstract nr 4764
  • CSchwerk, KSchulze-Osthoff. Regulation of apoptosis by alternative pre-mRNA splicing. Mol Cell 2005;19:1-13
  • CJDavid, JLManley. Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged. Genes Dev 2010;24:2343-64
  • LCorsini, SBonnal, SBonna, et al. U2AF-homology motif interactions are required for alternative splicing regulation by SPF45. Nat Struct Mol Biol 2007;14:620-9
  • FVégran, RMary, AGibeaud, et al. Survivin-3B potentiates immune escape in cancer but also inhibits the toxicity of cancer chemotherapy. Cancer Res 2013;73:5391-401
  • ASMoore, TAAlonzo, RBGerbing, et al. BIRC5 (Survivin) Splice Variant Expression Correlates With Refractory Disease and Poor Outcome in Pediatric Acute Myeloid Leukemia: a Report From the Children ’ s Oncology Group. Pediatr Blood Cancer 2014;61:647-52
  • MStark, CWichman, IAvivi, YGAssaraf. Aberrant splicing of folylpolyglutamate synthetase as a novel mechanism of antifolate resistance in leukemia. Blood 2009;113:4362-9
  • MStark, EEBram, MAkerman, et al. Heterogeneous nuclear ribonucleoprotein H1/H2-dependent unsplicing of thymidine phosphorylase results in anticancer drug resistance. J Biol Chem 2011;286:3741-54
  • MVeuger, MHonders, JLandegent, et al. High incidence of alternatively spliced forms of deoxycytidine kinase in patients with resistant acute myeloid leukemia. Blood 2000;96:1517-24
  • MJVeuger. Functional role of alternatively spliced deoxycytidine kinase in sensitivity to cytarabine of acute myeloid leukemic cells. Blood 2002;99:1373-80
  • JCai, VLDamaraju, NGroulx, et al. Two distinct molecular mechanisms underlying cytarabine resistance in human leukemic cells. Cancer Res 2008;68:2349-57
  • RHOakley, JACidlowski. Cellular processing of the glucocorticoid receptor gene and protein: new mechanisms for generating tissue-specific actions of glucocorticoids. J Biol Chem 2011;286:3177-84
  • SVandevyver, LDejager, CLibert. Comprehensive overview of the structure and regulation of the glucocorticoid receptor. Endocr Rev 2014;35:671-93
  • XHe, PEe, JCoon, WBeck. Alternative splicing of the multidrug resistance protein 1/ATP binding cassette transporter subfamily gene in ovarian cancer creates functional splice variants. Clin Cancer Res 2004;10:4652-60
  • JSampath, PRLong, RLShepard, et al. Human SPF45, a splicing factor, has limited expression in normal tissues, is overexpressed in many tumors, and can confer a multidrug-resistant phenotype to cells. Am J Pathol 2003;163:1781-90
  • WLPerry, RLShepard, JSampath, et al. Human splicing factor SPF45 (RBM17) confers broad multidrug resistance to anticancer drugs when overexpressed--a phenotype partially reversed by selective estrogen receptor modulators. Cancer Res 2005;65:6593-600
  • STEblen. Regulation of chemoresistance via alternative messenger RNA splicing. Biochem Pharmacol 2012;83:1063-72
  • QXu, DYLeung, KOKisich. Serine-arginine-rich protein p30 directs alternative splicing of glucocorticoid receptor pre-mRNA to glucocorticoid receptor beta in neutrophils. J Biol Chem 2003;278:27112-18
  • SGout, EBrambilla, ABoudria, et al. Abnormal expression of the pre-mRNA splicing regulators SRSF1, SRSF2, SRPK1 and SRPK2 in non small cell lung carcinoma. PLoS One 2012;7:e46539
  • GMHayes, PECarrigan, AMBeck, LJMiller. Targeting the RNA splicing machinery as a novel treatment strategy for pancreatic carcinoma. Cancer Res 2006;66:3819-27
  • MDe Wit, HKant, SRPiersma, et al. Colorectal cancer candidate biomarkers identified by tissue secretome proteome profiling. J Proteomics 2014;99:26-39
  • BJTauro, RAMathias, DWGreening, et al. Oncogenic H-ras reprograms Madin-Darby canine kidney (MDCK) cell-derived exosomal proteins following epithelial-mesenchymal transition. Mol Cell Proteomics 2013;12:2148-59
  • TBSchaaij-Visser, Mde Wit, SWLam, CRJimenez. The cancer secretome, current status and opportunities in the lung, breast and colorectal cancer context. Biochim Biophys Acta 2013;1834:2242-58
  • SBonnal, LVigevani, JValcárcel. The spliceosome as a target of novel antitumour drugs. Nat Rev Drug Discov 2012;11:847-59
  • YKotake, KSagane, TOwa, et al. Splicing factor SF3b as a target of the antitumor natural product pladienolide. Nat Chem Biol 2007;3:570-5
  • DKaida, HMotoyoshi, ETashiro, et al. Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA. Nat Chem Biol 2007;3:576-83
  • YGao, KKoide. Chemical perturbation of Mcl-1 pre-mRNA splicing to induce apoptosis in cancer cells. ACS Chem Biol 2013;8:895-900
  • BAlbert, PMcPherson, KO’Brien, et al. Meayamycin inhibits pre-messenger RNA splicing and exhibits picomolar activity against multidrug-resistant cells. Mol Cancer Ther 2009;8:2308-18
  • YGao, STrivedi, RLFerris, KKoide. Regulation of HPV16 E6 and MCL1 by SF3B1 inhibitor in head and neck cancer cells. Sci Rep 2014;4:6098
  • LFan, CLagisetti, CEdwards. Sudemycins, novel small molecule analogues of FR901464, induce alternative gene splicing. ACS Chem Biol 2011;6:582-9
  • PConvertini, MShen, PMPotter, et al. Sudemycin E influences alternative splicing and changes chromatin modifications. Nucleic Acids Res 2014;42:4947-61
  • WHChang, TCLiu, WKYang, et al. Amiloride modulates alternative splicing in leukemic cells and resensitizes Bcr-AblT315I mutant cells to imatinib. Cancer Res 2011;71:383-92
  • MBBull, JHLaragh. Amiloride: a Potassium-Sparing Natriuretic Agent. Circulation 1968;37:45-53
  • JGChang, DMYang, WHChang, et al. Small molecule amiloride modulates oncogenic RNA alternative splicing to devitalize human cancer cells. PLoS One 2011;6:e18643
  • FAEskens, FJRamos, HBurger, et al. Phase I pharmacokinetic and pharmacodynamic study of the first-in-class spliceosome inhibitor E7107 in patients with advanced solid tumors. Clin Cancer Res 2013;19:6296-304
  • DSHong, RKurzrock, ANaing, et al. A phase I, open-label, single-arm, dose-escalation study of E7107, a precursor messenger ribonucleic acid (pre-mRNA) splicesome inhibitor administered intravenously on days 1 and 8 every 21 days to patients with solid tumors. Invest New Drugs 2014;32:436-44
  • JBauman, RKole. Modulation of RNA splicing as a potential treatment for cancer. Bioeng Bugs 2011;2:125-8
  • PSpitali, AAartsma-Rus. Splice modulating therapies for human disease. Cell 2012;148:1085-8
  • AGDouglas, MJWood. RNA splicing: disease and therapy. Brief Funct Genomics 2011;10:151-64
  • FZammarchi, Ede Stanchina, EBournazou, et al. Antitumorigenic potential of STAT3 alternative splicing modulation. Proc Natl Acad Sci U S A 2011;108:17779-84
  • JABauman, SDLi, AYang, et al. Anti-tumor activity of splice-switching oligonucleotides. Nucleic Acids Res 2010;38:8348-56
  • TONielsen, SSorensen, FDagnæs-Hansen, et al. Directing HER4 mRNA expression towards the CYT2 isoform by antisense oligonucleotide decreases growth of breast cancer cells in vitro and in vivo. Br J Cancer 2013;108:2291-8
  • JWKotula, EDPratico, XMing, et al. Aptamer-mediated delivery of splice-switching oligonucleotides to the nuclei of cancer cells. Nucleic Acid Ther 2012;22:187-95
  • ONakagawa, XMing, KCarver, RJuliano. Conjugation with receptor-targeted histidine-rich peptides enhances the pharmacological effectiveness of antisense oligonucleotides. Bioconjug Chem 2014;25:165-70
  • PMoreno, APêgo, JLavoie. Therapeutic antisense oligonucleotides against cancer: hurdling to the clinic. Front Chem 2014;2:87
  • JRMendell, LRRodino-Klapac, ZSahenk, et al. Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol 2013;74:637-47
  • BEbert, OABernard. Mutations in RNA splicing machinery in human cancers. N Engl J Med 2011;365:2534-5
  • APawellek, SMcElroy, TSamatov, et al. Identification of small molecule inhibitors of pre-mRNA splicing. J Biol Chem 2014;289(30):20813-23
  • LShkreta, UFroehlich, ÉRPaquet, et al. Anticancer drugs affect the alternative splicing of Bcl-x and other human apoptotic genes. Mol Cancer Ther 2008;7:1398-409
  • JZhu, JGong, OGoodman Jr, et al. Bombesin attenuates pre-mRNA splicing of glucocorticoid receptor by regulating the expression of serine-arginine protein p30c (SRp30c) in prostate cancer cells. Biochim Biophys Acta 2007;1773:1087-94
  • YXu, AKarlsson, MJohansson. Identification of genes associated to 2’,2’-difluorodeoxycytidine resistance in HeLa cells with a lentiviral short-hairpin RNA library. Biochem Pharmacol 2011;82:210-15
  • XLiu, SBiswas, MGBerg, et al. Genomics-guided discovery of thailanstatins A, B, and C As pre-mRNA splicing inhibitors and antiproliferative agents from Burkholderia thailandensis MSMB43. J Nat Prod 2013;76:685-93

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