Genotoxic stress inhibits ewing sarcoma cell growth by modulating alternative pre-mRNA processing of the RNA helicase DHX9

Oncotarget

Volumn 6, Issue 31, 2015, Pages 31740-31757

  Fidaleo, Marco ^a,b   Svetoni, Francesca ^a,b   Volpe, Elisabetta ^b   Miñana, Belén ^c,d   Caporossi, Daniela ^a   Paronetto, Maria Paola ^a,b  

^a UNIVERSITY OF ROME FORO ITALICO   (Italy)

^b IRCCS FONDAZIONE SANTA LUCIA   (Italy)

^c CENTRE FOR GENOMIC REGULATION CRG   (Spain)

^d UNIVERSITAT POMPEU FABRA   (Spain)

Author keywords

Alternative splicing; DHX9; DNA damage; Ewing sarcoma

Indexed keywords

DHX9 PROTEIN; ETOPOSIDE; FLI1 PROTEIN; MESSENGER RNA PRECURSOR; RNA BINDING PROTEIN EWS; RNA HELICASE; RNA POLYMERASE II; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG; DEAD BOX PROTEIN; DHX9 PROTEIN, HUMAN; EWS-FLI FUSION PROTEIN; GYRASE INHIBITOR; MESSENGER RNA; ONCOPROTEIN; RNA PRECURSOR; TRANSCRIPTION FACTOR FLI 1; TUMOR PROTEIN;

ARTICLE; CANCER INHIBITION; CELL GROWTH; CONTROLLED STUDY; DHX9 GENE; DOWN REGULATION; ENZYME PHOSPHORYLATION; EWING SARCOMA; GENE; GENOTOXICITY; HUMAN; HUMAN CELL; RADIOSENSITIZATION; RNA PROCESSING; RNA SPLICING; SARCOMA CELL; STRESS; ULTRAVIOLET RADIATION; ALTERNATIVE RNA SPLICING; BONE NEOPLASMS; CELL PROLIFERATION; CELL SURVIVAL; DNA DAMAGE; DRUG EFFECTS; ENZYMOLOGY; GENE EXPRESSION REGULATION; GENETIC TRANSFECTION; GENETICS; METABOLISM; PATHOLOGY; PHOSPHORYLATION; RADIATION RESPONSE; SARCOMA, EWING; SIGNAL TRANSDUCTION; TIME FACTOR; TUMOR CELL LINE;

ALTERNATIVE SPLICING; BONE NEOPLASMS; CELL LINE, TUMOR; CELL PROLIFERATION; CELL SURVIVAL; DEAD-BOX RNA HELICASES; DNA DAMAGE; ETOPOSIDE; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; NEOPLASM PROTEINS; ONCOGENE PROTEINS, FUSION; PHOSPHORYLATION; PROTO-ONCOGENE PROTEIN C-FLI-1; RNA POLYMERASE II; RNA PRECURSORS; RNA, MESSENGER; RNA-BINDING PROTEIN EWS; SARCOMA, EWING; SIGNAL TRANSDUCTION; TIME FACTORS; TOPOISOMERASE II INHIBITORS; TRANSFECTION; ULTRAVIOLET RAYS;

EID: 84945582553     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.5033     Document Type: Article

References (53)

1. Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G, Aurias A, Thomas G. Gene fusion with an ETS DNAbinding domain caused by chromosome translocation in human tumours. Nature. 1992; 359:162-5.
2. Riggi N, Stamenkovic I. The Biology of Ewing sarcoma. Cancer Lett. 2007; 254:1-10.
3. Jedlicka P. Ewing Sarcoma, an enigmatic malignancy of likely progenitor cell origin, driven by transcription factor oncogenic fusions. Int J Clin Exp Pathol. 2010; 3:338-47.
4. Sanchez G, Bittencourt D, Laud K, Barbier J, Delattre O, Auboeuf D, Dutertre M. Alteration of cyclin D1 transcript elongation by a mutated transcription factor up-regulates the oncogenic D1b splice isoform in cancer. Proc Natl Acad Sci U S A. 2008; 105:6004-9.
5. Paronetto MP. Ewing sarcoma protein: a key player in human cancer. Int J Cell Biol. 2013; 2013:642853.
6. Sanchez G, Delattre O, Auboeuf D, Dutertre M. Coupled alteration of transcription and splicing by a single oncogene: boosting the effect on cyclin D1 activity. Cell Cycle. 2008; 7:2299-305.
7. Dutertre M, Sanchez G, De Cian MC, Barbier J, Dardenne E, Gratadou L, Dujardin G, Le Jossic-Corcos C, Corcos L, Auboeuf D. Cotranscriptional exon skipping in the genotoxic stress response. Nat Struct Mol Biol. 2010; 17:1358-66.
8. Paronetto MP, Minana B, Valcarcel J. The Ewing sarcoma protein regulates DNA damage-induced alternative splicing. Mol Cell. 2011; 43:353-68.
9. Paronetto MP, Bernardis I, Volpe E, Bechara E, Sebestyen E, Eyras E, Valcárcel J. Regulation of FAS exon definition and apoptosis by the Ewing sarcoma protein. Cell Rep. 2014; 7:1211-26.
10. Li H, Watford W, Li C, Parmelee A, Bryant MA, Deng C, O'Shea J, Bong Lee S. Ewing sarcoma gene EWS is essential for meiosis and B lymphocyte development. J Clin Invest. 2007; 117:1314-23.
11. Hurov KE, Cotta-Ramusino C, Elledge SJ. A genetic screen identifies the Triple T complex required for DNA damage signaling and ATM and ATR stability. Genes Dev. 2010; 24:1939-50.
12. O'Connell BC, Adamson B, Lydeard JR, Sowa ME, Ciccia A, Bredemeyer AL, Schlabach M, Gygi SP, Elledge SJ, Harper JW. A genome-wide camptothecin sensitivity screen identifies a mammalian MMS22L-NFKBIL2 complex required for genomic stability. Mol Cell. 2010; 40:645-57.
13. Biamonti G, Caceres JF. Cellular stress and RNA splicing. Trends Biochem Sci. 2009; 34:146-53.
14. Munoz MJ, Perez Santangelo MS, Paronetto MP, de la Mata M, Pelisch F, Boireau S, Glover-Cutter K, Ben-Dov C, Blaustein M, Lozano JJ, Bird G, Bentley D, Bertrand E, Kornblihtt ARl. DNA damage regulates alternative splicing through inhibition of RNA polymerase II elongation. Cell. 2009; 137:708-20.
15. David CJ, Manley JL. Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged. Genes Dev. 2010; 24:2343-64.
16. Bonnal S, Vigevani L, Valcarcel J. The spliceosome as a target of novel antitumour drugs. Nat Rev Drug Discov. 2012; 11:847-59.
17. Toretsky JA, Erkizan V, Levenson A, Abaan OD, Parvin JD, Cripe TP, Rice AM, Bong Lee S, Üren A. Oncoprotein EWS-FLI1 activity is enhanced by RNA helicase A. Cancer Res. 2006; 66:5574-81.
18. Bagnara GP, Serra M, Giovannini M, Badiali M, Stella M, Montaldi A, Tessarollo L, Cavazzana AO. Establishment and characterization of a primitive neuroectodermal tumor of bone continuous cell line (LAP-35). Int J Cell Cloning. 1990; 8:409-24.
19. Whang-Peng J, Triche TJ, Knutsen T, Miser J, KaoShan S, Tsai S, Israel MA. Cytogenetic characterization of selected small round cell tumors of childhood. Cancer Genet Cytogenet. 1986; 21:185-208.
20. Corrionero A, Minana B, Valcarcel J. Reduced fidelity of branch point recognition and alternative splicing induced by the anti-tumor drug spliceostatin A. Genes Dev. 2011; 25:445-59.
21. Nakajima T, Uchida C, Anderson SF, Lee CG, Hurwitz J, Parvin JD, Montminy M. RNA helicase A mediates association of CBP with RNA polymerase II. Cell. 1997; 90:1107-12.
22. Azzalin CM, Lingner J. The double life of UPF1 in RNA and DNA stability pathways. Cell Cycle. 2006; 5:1496-8.
23. Valacca C, Bonomi S, Buratti E, Pedrotti S, Baralle FE, Sette C, Ghigna C, Biamonti G. Sam68 regulates EMT through alternative splicing-activated nonsense-mediated mRNA decay of the SF2/ASF proto-oncogene. J Cell Biol. 2010; 191:87-99.
24. Takeda Y, Caudell P, Grady G, Wang G, Suwa A, Sharp GC, Dynan WS, Hardin JA. Human RNA helicase A is a lupus autoantigen that is cleaved during apoptosis. J Immunol. 1999; 163:6269-74.
25. Rockx DA, Mason R, van Hoffen A, Barton MC, Citterio E, Bregman DB, van Zeeland AA, Vrieling H, Mullenders LHF. UV-induced inhibition of transcription involves repression of transcription initiation and phosphorylation of RNA polymerase II. Proc Natl Acad Sci U S A. 2000; 97:10503-8.
26. Somesh BP, Reid J, Liu WF, Sogaard TM, ErdjumentBromage H, Tempst P, Svejstrup JQ. Multiple mechanisms confining RNA polymerase II ubiquitylation to polymerases undergoing transcriptional arrest. Cell. 2005; 121:913-23.
27. Laybourn PJ, Dahmus ME. Transcription-dependent structural changes in the C-terminal domain of mammalian RNA polymerase subunit IIa/o. J Biol Chem. 1989; 264:6693-8.
28. Shukla S, Oberdoerffer S. Co-transcriptional regulation of alternative pre-mRNA splicing. Biochim Biophys Acta. 2012; 1819:673-83.
29. Kornblihtt AR, Schor IE, Allo M, Dujardin G, Petrillo E, Munoz MJ. Alternative splicing: a pivotal step between eukaryotic transcription and translation. Nat Rev Mol Cell Biol. 2013; 14:153-65.
30. Batsche E, Yaniv M, Muchardt C. The human SWI/SNF subunit Brm is a regulator of alternative splicing. Nat Struct Mol Biol. 2006; 13:22-9.
31. Hsin JP, Manley JL. The RNA polymerase II CTD coordinates transcription and RNA processing. Genes Dev. 2012; 26:2119-37.
32. Marshall NF, Peng J, Xie Z, Price DH. Control of RNA polymerase II elongation potential by a novel carboxyl-terminal domain kinase. J Biol Chem. 1996; 271:27176-83.
33. Ip JY, Schmidt D, Pan Q, Ramani AK, Fraser AG, Odom DT, Blencowe BJ. Global impact of RNA polymerase II elongation inhibition on alternative splicing regulation. Genome Res. 2011; 21:390-401.
34. Fukuma M, Okita H, Hata J, Umezawa A. Upregulation of Id2, an oncogenic helix-loop-helix protein, is mediated by the chimeric EWS/ets protein in Ewing sarcoma. Oncogene. 2003; 22:1-9.
35. Erkizan HV, Kong Y, Merchant M, Schlottmann S, Barber-Rotenberg JS, Yuan L, Abaan OD, Chou TH, Dakshanamurthy S, Brown ML, Uren A, Toretsky JA. A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase A inhibits growth of Ewing's sarcoma. Nat Med. 2009; 15:750-6.
36. Patel SR. New agents in the treatment of soft-tissue sarcomas. Expert Opin Investig Drugs. 2000; 9:1545-51.
37. Starita LM, Horwitz AA, Keogh MC, Ishioka C, Parvin JD, Chiba N. BRCA1/BARD1 ubiquitinate phosphorylated RNA polymerase II. J Biol Chem. 2005; 280:24498-505.
38. Dujardin G, Lafaille C, de la Mata M, Marasco LE, Munoz MJ, Le Jossic-Corcos C, Corcos L, Kornblihtt AR. How slow RNA polymerase II elongation favors alternative exon skipping. Mol Cell. 2014; 54:683-90.
39. Linder P, Lasko PF, Ashburner M, Leroy P, Nielsen PJ, Nishi K, Schnier J, Slonimski PP. Birth of the D-E-A-D box. Nature. 1989; 337:121-2.
40. Rocak S, Linder P. DEAD-box proteins: the driving forces behind RNA metabolism. Nat Rev Mol Cell Biol. 2004; 5:232-41.
41. Lee CG, da Costa Soares V, Newberger C, Manova K, Lacy E, Hurwitz J. RNA helicase A is essential for normal gastrulation. Proc Natl Acad Sci U S A. 1998; 95:13709-13.
42. Jain A, Bacolla A, Chakraborty P, Grosse F, Vasquez KM. Human DHX9 helicase unwinds triple-helical DNA structures. Biochemistry. 2010; 49:6992-9.
43. Jain A, Bacolla A, Del Mundo IM, Zhao J, Wang G, Vasquez KM. DHX9 helicase is involved in preventing genomic instability induced by alternatively structured DNA in human cells. Nucleic Acids Res. 2013;.
44. Mills JR, Malina A, Lee T, Di Paola D, Larsson O, Miething C, Grosse F, Tang H, Zannis-Hadjopoulos M, Lowe SW, Pelletier J. RNAi screening uncovers Dhx9 as a modifier of ABT-737 resistance in an Emu-myc/Bcl-2 mouse model. Blood. 2013; 121:3402-12.
45. Friedemann J, Grosse F, Zhang S. Nuclear DNA helicase II (RNA helicase A) interacts with Werner syndrome helicase and stimulates its exonuclease activity. J Biol Chem. 2005; 280:31303-13.
46. Schlegel BP, Starita LM, Parvin JD. Overexpression of a protein fragment of RNA helicase A causes inhibition of endogenous BRCA1 function and defects in ploidy and cytokinesis in mammary epithelial cells. Oncogene. 2003; 22:983-91.
47. Christmann M, Tomicic MT, Origer J, Aasland D, Kaina B. c-Fos is required for excision repair of UV-light induced DNA lesions by triggering the re-synthesis of XPF. Nucleic Acids Res. 2006; 34:6530-9.
48. Grier HE, Krailo MD, Tarbell NJ, Link MP, Fryer CJ, Pritchard DJ, Gebhardt MC, Dickman PS, Perlman EJ, Meyers PA, Donaldson SS, Moore S, Rausen AR, Vietti TJ, Miser JS. Addition of ifosfamide and etoposide to standard chemotherapy for Ewing's sarcoma and primitive neuroectodermal tumor of bone. N Engl J Med. 2003; 348:694-701.
49. Hu-Lieskovan S, Heidel JD, Bartlett DW, Davis ME, Triche TJ. Sequence-specific knockdown of EWS-FLI1 by targeted, nonviral delivery of small interfering RNA inhibits tumor growth in a murine model of metastatic Ewing's sarcoma. Cancer Res. 2005; 65:8984-92.
50. Kovar H, Ban J, Pospisilova S. Potentials for RNAi in sarcoma research and therapy: Ewing's sarcoma as a model. Semin Cancer Biol. 2003; 13:275-81.
51. Dudoit S, Gentleman RC, Quackenbush J. Open source software for the analysis of microarray data. Biotechniques. 2003; Mar :45-51.
52. Ritchie ME, Silver J, Oshlack A, Holmes M, Diyagama D, Holloway A, Smyth GK. A comparison of background correction methods for two-colour microarrays. Bioinformatics. 2007; 23:2700-7.
53. Yang YW, Dudoit S, Luu P, Speed T. Normalization for cDNA Microarray Data. San Jose, California: SPIE BiOS2001.