Misregulation of pre-mRNA alternative splicing in cancer

Cancer Discovery

Volumn 3, Issue 11, 2013, Pages 1228-1237

  Zhang, Jian ^a   Manley, James L ^a  

^a Howard Hughes Medical Institute   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

B RAF KINASE; CYCLIN DEPENDENT KINASE INHIBITOR 1B; FIBROBLAST GROWTH FACTOR 1; ISOPROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN BCL XL; PROTEIN KINASE SYK; PROTEIN MDM2; PROTEIN TYROSINE KINASE; PYRUVATE KINASE; STAT2 PROTEIN; VASCULOTROPIN; VEMURAFENIB;

ALTERNATIVE RNA SPLICING; ANGIOGENESIS; APOPTOSIS; CANCER GROWTH; CARCINOGENESIS; CHRONIC LYMPHATIC LEUKEMIA; EXON SKIPPING; GENE CASSETTE; GENE MUTATION; GENE OVEREXPRESSION; GLYCOLYSIS; HUMAN; INTRON RETENTION; NEOPLASM; NONHUMAN; OVARY CANCER; PROTEOMICS; RECEPTOR DOWN REGULATION; RECEPTOR UPREGULATION; REVIEW; RNA INTERFERENCE;

ALTERNATIVE SPLICING; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MUTATION; NEOPLASMS; PHENOTYPE; REGULATORY ELEMENTS, TRANSCRIPTIONAL; RNA PRECURSORS; RNA-BINDING PROTEINS;

EID: 84887460995     PISSN: 21598274     EISSN: 21598290     Source Type: Journal    
DOI: 10.1158/2159-8290.CD-13-0253     Document Type: Review

References (102)

1. Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L, Mayr C, et al. Alternative isoform regulation in human tissue transcriptomes. Nature 2008; 456: 470-6.
2. Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet 2008; 40: 1413-5.
3. Leoni G, Le Pera L, Ferre F, Raimondo D, Tramontano A. Coding potential of the products of alternative splicing in human. Genome Biol 2011; 12: R9.
4. David CJ, Manley JL. Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged. Genes Dev 2010; 24: 2343-64.
5. Kelemen O, Convertini P, Zhang Z, Wen Y, Shen M, Falaleeva M, et al. Function of alternative splicing. Gene 2013; 514: 1-30.
6. Nilsen TW, Graveley BR. Expansion of the eukaryotic proteome by alternative splicing. Nature 2010; 463: 457-63.
7. Bland CS, Wang ET, Vu A, David MP, Castle JC, Johnson JM, et al. Global regulation of alternative splicing during myogenic differentiation. Nucleic Acids Res 2010; 38: 7651-64.
8. Johnson MB, Kawasawa YI, Mason CE, Krsnik Z, Coppola G, Bogdanovic D, et al. Functional and evolutionary insights into human brain development through global transcriptome analysis. Neuron 2009; 62: 494-509.
9. He C, Zhou F, Zuo Z, Cheng H, Zhou R. A global view of cancer-specific transcript variants by subtractive transcriptome-wide analysis. PLoS ONE 2009; 4: e4732.
10. Venables JP, Klinck R, Bramard A, Inkel L, Dufresne-Martin G, Koh C, et al. Identification of alternative splicing markers for breast cancer. Cancer Res 2008; 68: 9525-31.
11. Shapiro IM, Cheng AW, Flytzanis NC, Balsamo M, Condeelis JS, Oktay MH, et al. An EMT-driven alternative splicing program occurs in human breast cancer and modulates cellular phenotype. PLoS Genet 2011; 7: e1002218.
12. Prinos P, Garneau D, Lucier JF, Gendron D, Couture S, Boivin M, et al. Alternative splicing of SYK regulates mitosis and cell survival. Nat Struct Mol Biol 2011; 18: 673-9.
13. Grosso AR, Martins S, Carmo-Fonseca M. The emerging role of splicing factors in cancer. EMBO Rep 2008; 9: 1087-93.
14. Cooper TA, Wan L, Dreyfuss G. RNA and disease. Cell 2009; 136: 777-93.
15. Chen M, Manley JL. Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches. Nat Rev Mol Cell Biol 2009; 10: 741-54.
16. Barbosa-Morais NL, Irimia M, Pan Q, Xiong HY, Gueroussov S, Lee LJ, et al. The evolutionary landscape of alternative splicing in vertebrate species. Science 2012; 338: 1587-93.
17. Merkin J, Russell C, Chen P, Burge CB. Evolutionary dynamics of gene and isoform regulation in Mammalian tissues. Science 2012; 338: 1593-9.
18. Gaudino G, Follenzi A, Naldini L, Collesi C, Santoro M, Gallo KA, et al. RON is a heterodimeric tyrosine kinase receptor activated by the HGF homologue MSP. EMBO J 1994; 13: 3524-32.
19. Wagh PK, Peace BE, Waltz SE. Met-related receptor tyrosine kinase Ron in tumor growth and metastasis. Adv Cancer Res 2008; 100: 1-33.
20. Ghigna C, Giordano S, Shen H, Benvenuto F, Castiglioni F, Comoglio PM, et al. Cell motility is controlled by SF2/ASF through alternative splicing of the Ron protooncogene. Mol Cell 2005; 20: 881-90.
21. Collesi C, Santoro MM, Gaudino G, Comoglio PM. A splicing variant of the RON transcript induces constitutive tyrosine kinase activity and an invasive phenotype. Mol Cell Biol 1996; 16: 5518-26.
22. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature 2002; 417: 949-54.
23. Poulikakos PI, Persaud Y, Janakiraman M, Kong X, Ng C, Moriceau G, et al. RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature 2011; 480: 387-90.
24. Coopman PJ, Do MT, Barth M, Bowden ET, Hayes AJ, Basyuk E, et al. The Syk tyrosine kinase suppresses malignant growth of human breast cancer cells. Nature 2000; 406: 742-7.
25. Feldman AL, Sun DX, Law ME, Novak AJ, Attygalle AD, Thorland EC, et al. Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas. Leukemia 2008; 22: 1139-43.
26. Buchner M, Fuchs S, Prinz G, Pfeifer D, Bartholome K, Burger M, et al. Spleen tyrosine kinase is overexpressed and represents a potential therapeutic target in chronic lymphocytic leukemia. Cancer Res 2009; 69: 5424-32.
27. Luangdilok S, Box C, Patterson L, Court W, Harrington K, Pitkin L, et al. Syk tyrosine kinase is linked to cell motility and progression in squamous cell carcinomas of the head and neck. Cancer Res 2007; 67: 7907-16.
28. Chao DT, Korsmeyer SJ. BCL-2 family: regulators of cell death. Annu Rev Immunol 1998; 16: 395-419.
29. Boise LH, Gonzalez-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, et al. bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell 1993; 74: 597-608.
30. Xerri L, Parc P, Brousset P, Schlaifer D, Hassoun J, Reed JC, et al. Predominant expression of the long isoform of Bcl-x (Bcl-xL) in human lymphomas. Br J Haematol 1996; 92: 900-6.
31. Olopade OI, Adeyanju MO, Safa AR, Hagos F, Mick R, Thompson CB, et al. Overexpression of BCL-x protein in primary breast cancer is associated with high tumor grade and nodal metastases. Cancer J Sci Am 1997; 3: 230-7.
32. Takehara T, Liu X, Fujimoto J, Friedman SL, Takahashi H. Expression and role of Bcl-xL in human hepatocellular carcinomas. Hepatology 2001; 34: 55-61.
33. Ma X, Zhao Y, Li Y, Lu H, He Y. Relevance of Bcl-x expression in different types of endometrial tissues. J Exp Clin Cancer Res 2010; 29: 14.
34. Keck PJ, Hauser SD, Krivi G, Sanzo K, Warren T, Feder J, et al. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 1989; 246: 1309-12.
35. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989; 246: 1306-9.
36. Biselli-Chicote PM, Oliveira AR, Pavarino EC, Goloni-Bertollo EM. VEGF gene alternative splicing: pro-and anti-angiogenic isoforms in cancer. J Cancer Res Clin Oncol 2012; 138: 363-70.
37. Kawamura H, Li X, Harper SJ, Bates DO, Claesson-Welsh L. Vascular endothelial growth factor (VEGF)-A165b is a weak in vitro agonist for VEGF receptor-2 due to lack of coreceptor binding and deficient regulation of kinase activity. Cancer Res 2008; 68: 4683-92.
38. Gough DJ, Levy DE, Johnstone RW, Clarke CJ. IFNgamma signalingdoes it mean JAK-STAT? Cytokine Growth Factor Rev 2008; 19: 383-94.
39. Goldstein D, Laszlo J. The role of interferon in cancer therapy: a current perspective. CA Cancer J Clin 1988; 38: 258-77.
40. Du Z, Fan M, Kim JG, Eckerle D, Lothstein L, Weiei L, et al. Interferonresistant Daudi cell line with a Stat2 defect is resistant to apoptosis induced by chemotherapeutic agents. J Biol Chem 2009; 284: 27808-15.
41. Warburg O. On the origin of cancer cells. Science 1956; 123: 309-14.
42. David CJ, Chen M, Assanah M, Canoll P, Manley JL. HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature 2010; 463: 364-8.
43. Clower CV, Chatterjee D, Wang Z, Cantley LC, Vander Heiden MG, Krainer AR. The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism. Proc Natl Acad Sci U S A 2010; 107: 1894-9.
44. Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 2008; 452: 230-3.
45. Momand J, Zambetti GP, Olson DC, George D, Levine AJ. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 1992; 69: 1237-45.
46. Bartel F, Taubert H, Harris LC. Alternative and aberrant splicing of MDM2 mRNA in human cancer. Cancer Cell 2002; 2: 9-15.
47. Haupt Y, Maya R, Kazaz A, Oren M. Mdm2 promotes the rapid degradation of p53. Nature 1997; 387: 296-9.
48. Kubbutat MH, Jones SN, Vousden KH. Regulation of p53 stability by Mdm2. Nature 1997; 387: 299-303.
49. Sigalas I, Calvert AH, Anderson JJ, Neal DE, Lunec J. Alternatively spliced mdm2 transcripts with loss of p53 binding domain sequences: transforming ability and frequent detection in human cancer. Nat Med 1996; 2: 912-7.
50. Manfredi JJ. The Mdm2-p53 relationship evolves: Mdm2 swings both ways as an oncogene and a tumor suppressor. Genes Dev 2010; 24: 1580-9.
51. Fu XD. The superfamily of arginine/serine-rich splicing factors. RNA 1995; 1: 663-80.
52. Graveley BR. Sorting out the complexity of SR protein functions. RNA 2000; 6: 1197-211.
53. Long JC, Caceres JF. The SR protein family of splicing factors: master regulators of gene expression. Biochem J 2009; 417: 15-27.
54. Martinez-Contreras R, Cloutier P, Shkreta L, Fisette JF, Revil T, Chabot B. hnRNP proteins and splicing control. Adv Exp Med Biol 2007; 623: 123-47.
55. Manley JL, Tacke R. SR proteins and splicing control. Genes Dev 1996; 10: 1569-79.
56. Karni R, de Stanchina E, Lowe SW, Sinha R, Mu D, Krainer AR. The gene encoding the splicing factor SF2/ASF is a proto-oncogene. Nat Struct Mol Biol 2007; 14: 185-93.
57. Anczukow O, Rosenberg AZ, Akerman M, Das S, Zhan L, Karni R, et al. The splicing factor SRSF1 regulates apoptosis and proliferation to promote mammary epithelial cell transformation. Nat Struct Mol Biol 2012; 19: 220-8.
58. Michlewski G, Sanford JR, Caceres JF. The splicing factor SF2/ASF regulates translation initiation by enhancing phosphorylation of 4E-BP1. Mol Cell 2008; 30: 179-89.
59. Das S, Anczukow O, Akerman M, Krainer AR. Oncogenic splicing factor SRSF1 is a critical transcriptional target of MYC. Cell Rep 2012; 1: 110-7.
60. Jia R, Li C, McCoy JP, Deng CX, Zheng ZM. SRp20 is a protooncogene critical for cell proliferation and tumor induction and maintenance. Int J Biol Sci 2010; 6: 806-26.
61. 1 cell cycle arrest and apoptosis in colon cancer cells. Oncogene 2013 Mar 18. [Epub ahead of print].
62. Tang Y, Horikawa I, Ajiro M, Robles AI, Fujita K, Mondal A M, et al. Downregulation of splicing factor SRSF3 induces p53beta, an alternatively spliced isoform of p53 that promotes cellular senescence. Oncogene 2013; 32: 2792-8.
63. Wang Z, Chatterjee D, Jeon HY, Akerman M, Vander Heiden MG, Cantley LC, et al. Exon-centric regulation of pyruvate kinase M alternative splicing via mutually exclusive exons. J Mol Cell Biol 2012; 4: 79-87.
64. Patry C, Bouchard L, Labrecque P, Gendron D, Lemieux B, Toutant J, et al. Small interfering RNA-mediated reduction in heterogeneous nuclear ribonucleoparticule A1/A2 proteins induces apoptosis in human cancer cells but not in normal mortal cell lines. Cancer Res 2003; 63: 7679-88.
65. Golan-Gerstl R, Cohen M, Shilo A, Suh SS, Bakacs A, Coppola L, et al. Splicing factor hnRNP A2/B1 regulates tumor suppressor gene splicing and is an oncogenic driver in glioblastoma. Cancer Res 2011; 71: 4464-72.
66. Huelga SC, Vu AQ, Arnold JD, Liang TY, Liu PP, Yan BY, et al. Integrative genome-wide analysis reveals cooperative regulation of alternative splicing by hnRNP proteins. Cell Rep 2012; 1: 167-78.
67. Chen M, David CJ, Manley JL. Concentration-dependent control of pyruvate kinase M mutually exclusive splicing by hnRNP proteins. Nat Struct Mol Biol 2012; 19: 346-54.
68. Xue Y, Zhou Y, Wu T, Zhu T, Ji X, Kwon YS, et al. G enome-wide analysis of PTB-RNA interactions reveals a strategy used by the general splicing repressor to modulate exon inclusion or skipping. Mol Cell 2009; 36: 996-1006.
69. Izaguirre DI, Zhu W, Hai T, Cheung HC, Krahe R, Cote GJ. PTBP1-dependent regulation of USP5 alternative RNA splicing plays a role in glioblastoma tumorigenesis. Mol Carcinog 2012; 51: 895-906.
70. He X, Pool M, Darcy KM, Lim SB, Auersperg N, Coon JS, et al. Knockdown of polypyrimidine tract-binding protein suppresses ovarian tumor cell growth and invasiveness in vitro. Oncogene 2007; 26: 4961-8.
71. Wang C, Norton JT, Ghosh S, Kim J, Fushimi K, Wu JY, et al. Polypyrimidine tract-binding protein (PTB) differentially affects malignancy in a cell line-dependent manner. J Biol Chem 2008; 283: 20277-87.
72. Jin W, Bruno IG, Xie TX, Sanger LJ, Cote GJ. Polypyrimidine tractbinding protein down-regulates fibroblast growth factor receptor 1 alpha-exon inclusion. Cancer Res 2003; 63: 6154-7.
73. Wang F, Kan M, Yan G, Xu J, McKeehan WL. Alternately spliced NH2-terminal immunoglobulin-like Loop I in the ectodomain of the fibroblast growth factor (FGF) receptor 1 lowers affinity for both heparin and FGF-1. J Biol Chem 1995; 270: 10231-5.
74. Yamaguchi F, Saya H, Bruner JM, Morrison RS. Differential expression of two fibroblast growth factor-receptor genes is associated with malignant progression in human astrocytomas. Proc Natl Acad Sci U S A 1994; 91: 484-8.
75. Dayal S, Sparks A, Jacob J, Allende-Vega N, Lane DP, Saville MK. Suppression of the deubiquitinating enzyme USP5 causes the accumulation of unanchored polyubiquitin and the activation of p53. J Biol Chem 2009; 284: 5030-41.
76. Llorian M, Schwartz S, Clark TA, Hollander D, Tan LY, Spellman R, et al. Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB. Nat Struct Mol Biol 2010; 17: 1114-23.
77. Lefave CV, Squatrito M, Vorlova S, Rocco GL, Brennan CW, Holland EC, et al. Splicing factor hnRNPH drives an oncogenic splicing switch in gliomas. EMBO J 2011; 30: 4084-97.
78. Mulherkar N, Prasad KV, Prabhakar BS. MADD/DENN splice variant of the IG20 gene is a negative regulator of caspase-8 activation. Knockdown enhances TRAIL-induced apoptosis of cancer cells. J Biol Chem 2007; 282: 11715-21.
79. Castello A, Fischer B, Eichelbaum K, Horos R, Beckmann BM, Strein C, et al. Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 2012; 149: 1393-406.
80. Barash Y, Calarco JA, Gao W, Pan Q, Wang X, Shai O, et al. Deciphering the splicing code. Nature 2010; 465: 53-9.
81. Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 2011; 478: 64-9.
82. Visconte V, Makishima H, Jankowska A, Szpurka H, Traina F, Jerez A, et al. SF3B1, a splicing factor is frequently mutated in refractory anemia with ring sideroblasts. Leukemia 2012; 26: 542-5.
83. Papaemmanuil E, Cazzola M, Boultwood J, Malcovati L, Vyas P, Bowen D, et al. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N Engl J Med 2011; 365: 1384-95.
84. Wang L, Lawrence MS, Wan Y, Stojanov P, Sougnez C, Stevenson K, et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med 2011; 365: 2497-506.
85. Rossi D, Bruscaggin A, Spina V, Rasi S, Khiabanian H, Messina M, et al. Mutations of the SF3B1 splicing factor in chronic lymphocytic leukemia: association with progression and fludarabine-refractoriness. Blood 2011; 118: 6904-8.
86. Quesada V, Conde L, Villamor N, Ordonez GR, Jares P, Bassaganyas L, et al. Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nat Genet 2012; 44: 47-52.
87. Harbour JW, Roberson ED, Anbunathan H, Onken MD, Worley LA, Bowcock AM. Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma. Nat Genet 2013; 45: 133-5.
88. Martin M, Masshofer L, Temming P, Rahmann S, Metz C, Bornfeld N, et al. Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with disomy 3. Nat Genet 2013; 45: 933-6.
89. Hicks MJ, Mueller WF, Shepard PJ, Hertel KJ. Competing upstream 555splice sites enhance the rate of proximal splicing. Mol Cell Biol 2010; 30: 1878-86.
90. Visconte V, Rogers HJ, Singh J, Barnard J, Bupathi M, Traina F, et al. SF3B1 haploinsufficiency leads to formation of ring sideroblasts in myelodysplastic syndromes. Blood 2012; 120: 3173-86.
91. Boultwood J, Pellagatti A, Nikpour M, Pushkaran B, Fidler C, Cattan H, et al. The role of the iron transporter ABCB7 in refractory anemia with ring sideroblasts. PLoS ONE 2008; 3: e1970.
92. Nikpour M, Scharenberg C, Liu A, Conte S, Karimi M, Mortera-Blanco T, et al. The transporter ABCB7 is a mediator of the phenotype of acquired refractory anemia with ring sideroblasts. Leukemia 2013; 27: 889-96.
93. Malcovati L, Papaemmanuil E, Bowen DT, Boultwood J, Della Porta MG, Pascutto C, et al. Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms. Blood 2011; 118: 6239-46.
94. Patnaik MM, Lasho TL, Hodnefield JM, Knudson RA, Ketterling RP, Garcia-Manero G, et al. SF3B1 mutations are prevalent in myelodysplastic syndromes with ring sideroblasts but do not hold independent prognostic value. Blood 2012; 119: 569-72.
95. Makishima H, Visconte V, Sakaguchi H, Jankowska AM, Abu Kar S, Jerez A, et al. Mutations in the spliceosome machinery, a novel and ubiquitous pathway in leukemogenesis. Blood 2012; 119: 3203-10.
96. Hirabayashi S, Flotho C, Moetter J, Heuser M, Hasle H, Gruhn B, et al. Spliceosomal gene aberrations are rare, coexist with oncogenic mutations, and are unlikely to exert a driver effect in childhood MDS and JMML. Blood 2012; 119: e96-9.
97. Schilling B, Bielefeld N, Sucker A, Hillen U, Zimmer L, Schadendorf D, et al. Lack of SF3B1 R625 mutations in cutaneous melanoma. Diagn Pathol 2013; 8: 87.
98. Kaida D, Schneider-Poetsch T, Yoshida M. Splicing in oncogenesis and tumor suppression. Cancer Sci 2012; 103: 1611-6.
99. Bonnal S, Vigevani L, Valcarcel J. The spliceosome as a target of novel antitumour drugs. Nat Rev Drug Discov 2012; 11: 847-59.
100. Webb TR, Joyner AS, Potter PM. The development and application of small molecule modulators of SF3b as therapeutic agents for cancer. Drug Discov Today 2013; 18: 43-9.
101. Kaida D, Motoyoshi H, Tashiro E, Nojima T, Hagiwara M, Ishigami K, et al. Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA. Nat Chem Biol 2007; 3: 576-83.
102. Furumai R, Uchida K, Komi Y, Yoneyama M, Ishigami K, Watanabe H, et al. Spliceostatin A blocks angiogenesis by inhibiting global gene expression including VEGF. Cancer Sci 2010; 101: 2483-9.