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

Expert Opinion on Drug Metabolism and Toxicology

Volumn 11, Issue 5, 2015, Pages 673-689

  Wojtuszkiewicz, Anna ^a   Assaraf, Yehuda G ^b   Maas, Marielle J P ^a   Kaspers, Gertjan J L ^a   Jansen, Gerrit ^a   Cloos, Jacqueline ^a  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^b TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

Author keywords

Cancer therapy; Drug resistance; Hematological malignancies; Oligonucleotides; Prognosis; Spliceosome; Splicing factors

Indexed keywords

CAPECITABINE; CARBOPLATIN; CIS ACTING ELEMENT; CISPLATIN; CYTARABINE; DOXORUBICIN; ETOPOSIDE; FLUDARABINE; FLUOROURACIL; GEMCITABINE; GLUCOCORTICOID; MITOXANTRONE; OLIGONUCLEOTIDE; PACLITAXEL; TRANS ACTING FACTOR; VINCRISTINE; ANTINEOPLASTIC AGENT; RNA PRECURSOR;

ALTERNATIVE RNA SPLICING; APOPTOSIS; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER PROGNOSIS; CANCER THERAPY; CARCINOGENESIS; CELL COMMUNICATION; CHROMATIN STRUCTURE; COLON CANCER; COLORECTAL CANCER; DRUG METABOLISM; DRUG RESISTANCE; EXON SKIPPING; EXOSOME; GENE MUTATION; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HUMAN; INTRON RETENTION; LEUKEMIA; LUNG CANCER; METASTATIC MELANOMA; MULTIDRUG RESISTANCE; NEOPLASM; NEUROBLASTOMA; NON SMALL CELL LUNG CANCER; NONHUMAN; OVARY CANCER; PATHOGENESIS; PROSTATE CANCER; REVIEW; RHABDOMYOSARCOMA; RNA SPLICING; SPLICEOSOME; TRANSCRIPTION REGULATION; TRIPLE NEGATIVE BREAST CANCER; UTERINE CERVIX CANCER; ANIMAL; GENETICS; MUTATION; NEOPLASMS; PATHOLOGY; PROGNOSIS;

ALTERNATIVE SPLICING; ANIMALS; ANTINEOPLASTIC AGENTS; CARCINOGENESIS; DRUG RESISTANCE, NEOPLASM; HUMANS; MUTATION; NEOPLASMS; PROGNOSIS; RNA PRECURSORS; SPLICEOSOMES;

EID: 84928898276     PISSN: 17425255     EISSN: 17447607     Source Type: Journal    
DOI: 10.1517/17425255.2015.993316     Document Type: Review

References (103)

1. Berget S, Moore C, Sharp P. Spliced segments at the 5' terminus of adenovirus 2 late mRNA. Proc Natl Acad Sci USA 1977;74:3171-5
2. Chow L, Gelinas R, Broker T, Roberts R. An amazing sequence arrangement at the 5' ends of adenovirus 2 messenger RNA. Cell 1977;12:1-8
3. Nilsen TW, Graveley BR. Expansion of the eukaryotic proteome by alternative splicing. Nature 2010;463:457-63
4. Chen M, Manley J. Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches. Nat Rev Mol Cell Biol 2009;10:741-54
5. Wahl MC, Will CL, Lührmann R. The spliceosome: design principles of a dynamic RNP machine. Cell 2009;136:701-18.
6. Sterner DA, Carlo T, Berget SM. Architectural limits on split genes. Proc Natl Acad Sci USA 1996;93:15081-5
7. Faustino NA, Cooper TA. Pre-mRNA splicing and human disease. Genes Dev 2003;17:419-37
8. Guttmacher A. Genomic medicine-a primer. N Enlg J Med 2002;347:1512-20
9. Will CL, Lührmann R. Spliceosome structure and function. Cold Spring Harb Perspect Biol 2011;3(7):a003707
10. Matlin AJ, Clark F, Smith CW. Understanding alternative splicing: towards a cellular code. Nat Rev Mol Cell Biol 2005;6:386-98
11. Lopez AJ. Alternative splicing of premRNA: developmental consequences and mechanisms of regulation. Annu Rev Genet 1998;32:279-305
12. Ghigna C, Valacca C, Biamonti G. Alternative splicing and tumor progression. Curr Genomics 2008;9:556-70
13. Fu XD, Ares M. Context-dependent control of alternative splicing by RNAbinding proteins. Nat Rev Genet 2014;15:689-701
14. Witten JT, Ule J. Understanding splicing regulation through RNA splicing maps. Trends Genet 2011;27:89-97
15. Li Q, Lee J-A, Black DL. Neuronal regulation of alternative pre-mRNA splicing. Nat Rev Neurosci 2007;8:819-31
16. Cartegni L, Chew SL, Krainer AR. Listening To Silence and Understanding Nonsense: exonic Mutations That Affect Splicing. Nat Rev Genet 2002;3:285-98
17. Bhatt DM, Pandya-Jones A, Tong AJ, et al. Transcript dynamics of proinflammatory genes revealed by sequence analysis of subcellular RNA fractions. Cell 2012;150:279-90
18. Tilgner H, Knowles DG, Johnson R, 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
19. Carrillo Oesterreich F, Preibisch S, Neugebauer KM. Global analysis of nascent RNA reveals transcriptional pausing in terminal exons. Mol Cell 2010;40:571-81
20. Rosonina E, Blencowe BJ. Gene expression: the close coupling of transcription and splicing. Curr Biol 2002;12(9):R319-21
21. David CJ, Boyne AR, Millhouse SR, Manley JL. The RNA polymerase II C-terminal domain promotes splicing activation through recruitment of a U2AF65-Prp19 complex. Genes Dev 2011;25:972-83
22. Carrillo Oesterreich F, Bieberstein N, Neugebauer KM. Pause locally, splice globally. Trends Cell Biol 2011;21:328-35
23. Wang GS, Cooper TA. Splicing in disease: disruption of the splicing code and the decoding machinery. Nat Rev Genet 2007;8:749-61
24. Kaida D, Schneider-Poetsch T, Yoshida M. Splicing in oncogenesis and tumor suppression. Cancer Sci 2012;103:1611-16
25. Bonomi S, Gallo S, Catillo M, et al. Oncogenic alternative splicing switches: role in cancer progression and prospects for therapy. Int J Cell Biol 2013;2013:962038
26. Srebrow A, Kornblihtt AR. The connection between splicing and cancer. J Cell Sci 2006;119:2635-41
27. Chen LL, Sabripour M, Wu EF, 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
28. Khoury MP, Bourdon JC. The isoforms of the p53 protein. Cold Spring Harb Perspect Biol 2010;2:a000927
29. Das S, Krainer AR. Emerging functions of SRSF1, splicing factor and oncoprotein, in RNA metabolism and cancer. Mol Cancer Res 2014;12:1195-204
30. Karni R, de Stanchina E, Lowe SW, et al. The gene encoding the splicing factor SF2/ASF is a proto-oncogene. Nat Struct Mol Biol 2007;14:185-93
31. Anczuków O, Rosenberg AZ, Akerman M, et al. The splicing factor SRSF1 regulates apoptosis and proliferation to promote mammary epithelial cell transformation. Nat Struct Mol Biol 2012;19:220-8
32. Grosso AR, Martins S, Carmo-Fonseca M. The emerging role of splicing factors in cancer. EMBO Rep 2008;9:1087-93
33. Brinkman BM. Splice variants as cancer biomarkers. Clin Biochem 2004;37:584-94
34. Jin W, McCutcheon I, Fuller G, et al. Fibroblast growth factor receptor-1 aexon exclusion and polypyrimidine tractbinding protein in glioblastoma multiforme tumors. Cancer Res 2000;60:1221-4
35. Wang Y, Chen D, Qian H, et al. The Splicing Factor RBM4 Controls Apoptosis, Proliferation, and Migration to Suppress Tumor Progression. Cancer Cell 2014;26:374-89
36. Adamia S, Haibe-Kains B. A genomewide aberrant RNA splicing in patients with acute myeloid leukemia identifies novel potential disease markers and therapeutic targets. Clin Cancer Res 2014;20:1135-45
37. Damm F, Nguyen-Khac F, Fontenay M, Bernard OA. Spliceosome and other novel mutations in chronic lymphocytic leukemia and myeloid malignancies. Leukemia 2012;26:2027-31.
38. Damm F, Kosmider O, Gelsi-Boyer V, et al. Mutations affecting mRNA splicing define distinct clinical phenotypes and correlate with patient outcome in myelodysplastic syndromes. Blood 2012;119:3211-18
39. Rossi D, Bruscaggin A, Spina V, et al. Mutations of the SF3B1 splicing factor in chronic lymphocytic leukemia: association with progression and fludarabine-refractoriness. Blood 2011;118:6904-8
40. Papaemmanuil E, Gerstung M, Malcovati L, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood 2013;122:3616-27
41. Visconte V, Makishima H, Maciejewski JP, Tiu R V. Emerging roles of the spliceosomal machinery in myelodysplastic syndromes and other hematological disorders. Leukemia 2012;26:2447-54
42. Malcovati L, Papaemmanuil E, Bowen DT, et al. Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms. Blood 2011;118:6239-46
43. Thol F, Kade S, Schlarmann C, et al. Frequency and prognostic impact of mutations in SRSF2, U2AF1, and ZRSR2 in patients with myelodysplastic syndromes. Blood 2012;119:3578-84
44. Graubert TA, Shen D, Ding L, et al. Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes. Nat Genet 2012;44:53-7
45. Kurtovic-Kozaric A, Przychodzen B, Singh J, et al. PRPF8 defects cause missplicing in myeloid malignancies. Leukemia 2014. [Epub ahead of print]
46. Yoshida K, Sanada M, Shiraishi Y, et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 2011;478:64-9
47. Kar SA, Jankowska A, Makishima H, 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
48. Itzykson R, Kosmider O, Renneville A, et al. Prognostic score including gene mutations in chronic myelomonocytic leukemia. J Clin Oncol 2013;31:2428-36
49. Patnaik MM, Lasho TL, Finke CM, 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
50. Meggendorfer M, Roller A, Haferlach T, et al. SRSF2 mutations in 275 cases with chronic myelomonocytic leukemia (CMML). Blood 2012;120:3080-8
51. Dehm SM. mRNA splicing variants: exploiting modularity to outwit cancer therapy. Cancer Res 2013;73:5309-14.
52. Wojtuszkiewicz A, Schuurhuis GJ, Kessler FL, et al. Transfer of regulatory protein networks via extracellular vesicles as a candidate mechanism of apoptosisresistance 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
53. Schwerk C, Schulze-Osthoff K. Regulation of apoptosis by alternative pre-mRNA splicing. Mol Cell 2005;19:1-13
54. David CJ, Manley JL. Alternative premRNA splicing regulation in cancer: pathways and programs unhinged. Genes Dev 2010;24:2343-64
55. Corsini L, Bonnal S, Bonna S, et al. U2AF-homology motif interactions are required for alternative splicing regulation by SPF45. Nat Struct Mol Biol 2007;14:620-9
56. Vegran F, Mary R, Gibeaud A, et al. Survivin-3B potentiates immune escape in cancer but also inhibits the toxicity of cancer chemotherapy. Cancer Res 2013;73:5391-401
57. Moore AS, Alonzo TA, Gerbing RB, 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
58. Stark M, Wichman C, Avivi I, Assaraf YG. Aberrant splicing of folylpolyglutamate synthetase as a novel mechanism of antifolate resistance in leukemia. Blood 2009;113:4362-9
59. Stark M, Bram EE, Akerman M, et al. Heterogeneous nuclear ribonucleoprotein H1/H2-dependent unsplicing of thymidine phosphorylase results in anticancer drug resistance. J Biol Chem 2011;286:3741-54
60. Veuger M, Honders M, Landegent J, et al. High incidence of alternatively spliced forms of deoxycytidine kinase in patients with resistant acute myeloid leukemia. Blood 2000;96:1517-24
61. Veuger MJ. Functional role of alternatively spliced deoxycytidine kinase in sensitivity to cytarabine of acute myeloid leukemic cells. Blood 2002;99:1373-80
62. Cai J, Damaraju VL, Groulx N, et al. Two distinct molecular mechanisms underlying cytarabine resistance in human leukemic cells. Cancer Res 2008;68:2349-57
63. Oakley RH, Cidlowski JA. 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
64. Vandevyver S, Dejager L, Libert C. Comprehensive overview of the structure and regulation of the glucocorticoid receptor. Endocr Rev 2014;35:671-93
65. He X, Ee P, Coon J, Beck W. 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
66. Sampath J, Long PR, Shepard RL, 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.
67. Perry WL, Shepard RL, Sampath J, 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
68. Eblen ST. Regulation of chemoresistance via alternative messenger RNA splicing. Biochem Pharmacol 2012;83:1063-72
69. Xu Q, Leung DY, Kisich KO. 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
70. Gout S, Brambilla E, Boudria A, 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
71. Hayes GM, Carrigan PE, Beck AM, Miller LJ. Targeting the RNA splicing machinery as a novel treatment strategy for pancreatic carcinoma. Cancer Res 2006;66:3819-27
72. De Wit M, Kant H, Piersma SR, et al. Colorectal cancer candidate biomarkers identified by tissue secretome proteome profiling. J Proteomics 2014;99:26-39
73. Tauro BJ, Mathias RA, Greening DW, 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
74. Schaaij-Visser TB, de Wit M, Lam SW, Jimenez CR. The cancer secretome, current status and opportunities in the lung, breast and colorectal cancer context. Biochim Biophys Acta 2013;1834:2242-58
75. Bonnal S, Vigevani L, Valcárcel J. The spliceosome as a target of novel antitumour drugs. Nat Rev Drug Discov 2012;11:847-59
76. Kotake Y, Sagane K, Owa T, et al. Splicing factor SF3b as a target of the antitumor natural product pladienolide. Nat Chem Biol 2007;3:570-5
77. Kaida D, Motoyoshi H, Tashiro E, et al. Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA. Nat Chem Biol 2007;3:576-83
78. Gao Y, Koide K. Chemical perturbation of Mcl-1 pre-mRNA splicing to induce apoptosis in cancer cells. ACS Chem Biol 2013;8:895-900
79. Albert B, McPherson P, O'Brien K, et al. Meayamycin inhibits pre-messenger RNA splicing and exhibits picomolar activity against multidrug-resistant cells. Mol Cancer Ther 2009;8:2308-18
80. Gao Y, Trivedi S, Ferris RL, Koide K. Regulation of HPV16 E6 and MCL1 by SF3B1 inhibitor in head and neck cancer cells. Sci Rep 2014;4:6098
81. Fan L, Lagisetti C, Edwards C. Sudemycins, novel small molecule analogues of FR901464, induce alternative gene splicing. ACS Chem Biol 2011;6:582-9
82. Convertini P, Shen M, Potter PM, et al. Sudemycin E influences alternative splicing and changes chromatin modifications. Nucleic Acids Res 2014;42:4947-61
83. Chang WH, Liu TC, Yang WK, et al. Amiloride modulates alternative splicing in leukemic cells and resensitizes Bcr-AblT315I mutant cells to imatinib. Cancer Res 2011;71:383-92
84. Bull MB, Laragh JH. Amiloride: a Potassium-Sparing Natriuretic Agent. Circulation 1968;37:45-53
85. Chang JG, Yang DM, Chang WH, et al. Small molecule amiloride modulates oncogenic RNA alternative splicing to devitalize human cancer cells. PLoS One 2011;6:e18643
86. Eskens FA, Ramos FJ, Burger H, 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
87. Hong DS, Kurzrock R, Naing A, et al. A phase I, open-label, single-arm, doseescalation 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
88. Bauman J, Kole R. Modulation of RNA splicing as a potential treatment for cancer. Bioeng Bugs 2011;2:125-8
89. Spitali P, Aartsma-Rus A. Splice modulating therapies for human disease. Cell 2012;148:1085-8
90. Douglas AG, Wood MJ. RNA splicing: disease and therapy. Brief Funct Genomics 2011;10:151-64
91. Zammarchi F, de Stanchina E, Bournazou E, et al. Antitumorigenic potential of STAT3 alternative splicing modulation. Proc Natl Acad Sci USA 2011;108:17779-84
92. Bauman JA, Li SD, Yang A, et al. Anti-tumor activity of splice-switching oligonucleotides. Nucleic Acids Res 2010;38:8348-56
93. Nielsen TO, Sorensen S, Dagnæs-Hansen F, 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
94. Kotula JW, Pratico ED, Ming X, et al. Aptamer-mediated delivery of spliceswitching oligonucleotides to the nuclei of cancer cells. Nucleic Acid Ther 2012;22:187-95
95. Nakagawa O, Ming X, Carver K, Juliano R. Conjugation with receptortargeted histidine-rich peptides enhances the pharmacological effectiveness of antisense oligonucleotides. Bioconjug Chem 2014;25:165-70
96. Moreno P, Pêgo A, Lavoie J. Therapeutic antisense oligonucleotides against cancer: hurdling to the clinic. Front Chem 2014;2:87
97. Mendell JR, Rodino-Klapac LR, Sahenk Z, et al. Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol 2013;74:637-47
98. Ebert B, Bernard OA. Mutations in RNA splicing machinery in human cancers. N Engl J Med 2011;365:2534-5
99. Pawellek A, McElroy S, Samatov T, et al. Identification of small molecule inhibitors of pre-mRNA splicing. J Biol Chem 2014;289(30):20813-23
100. Shkreta L, Froehlich U, Paquet É R, et al. Anticancer drugs affect the alternative splicing of Bcl-x and other human apoptotic genes. Mol Cancer Ther 2008;7:1398-409
101. Zhu J, Gong J, Goodman Jr O, 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
102. Xu Y, Karlsson A, Johansson M. 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
103. Liu X, Biswas S, Berg MG, 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