Three Prime Repair Exonuclease 1 (TREX1) expression correlates with cervical cancer cells growth in vitro and disease progression in vivo

Carregando...
Imagem de Miniatura
Citações na Scopus
14
Tipo de produção
article
Data de publicação
2019
Título da Revista
ISSN da Revista
Título do Volume
Editora
NATURE PUBLISHING GROUP
Autores
PRATI, Bruna
ABJAUDE, Walason da Silva
HERBSTER, Suellen
RABELO-SANTOS, Silvia Helena
ZEFERINO, Luiz Carlos
Citação
SCIENTIFIC REPORTS, v.9, article ID 351, 14p, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Alterations in specific DNA damage repair mechanisms in the presence of human papillomavirus (HPV) infection have been described in different experimental models. However, the global effect of HPV on the expression of genes involved in these pathways has not been analyzed in detail. In the present study, we compared the expression profile of 135 genes involved in DNA damage repair among primary human keratinocytes (PHK), HPV-positive (SiHa and HeLa) and HPV-negative (C33A) cervical cancer derived cell lines. We identified 9 genes which expression pattern distinguishes HPV-positive tumor cell lines from C33A. Moreover, we observed that Three Prime Repair Exonuclease 1 (TREX1) expression is upregulated exclusively in HPV-transformed cell lines and PHK expressing HPV16 E6 and E7 oncogenes. We demonstrated that TREX1 silencing greatly affects tumor cells clonogenic and anchorage independent growth potential. We showed that this effect is associated with p53 upregulation, accumulation of subG1 cells, and requires the expression of E7 from high-risk HPV types. Finally, we observed an increase in TREX1 levels in precancerous lesions, squamous carcinomas and adenocarcinomas clinical samples. Altogether, our results indicate that TREX1 upregulation is important for cervical tumor cells growth and may contribute with tumor establishment and progression.
Palavras-chave
Referências
  1. Akerman GS, 2001, CANCER RES, V61, P3837
  2. Alazawi W, 2004, BRIT J CANCER, V91, P2063, DOI 10.1038/sj.bjc.6602237
  3. Arias-Pulido Hugo, 2002, Mol Cancer, V1, P3, DOI 10.1186/1476-4598-1-3
  4. Bajpai D, 2013, MOL CELL BIOCHEM, V377, P45, DOI 10.1007/s11010-013-1569-y
  5. Baldwin A, 2008, P NATL ACAD SCI USA, V105, P16478, DOI 10.1073/pnas.0806195105
  6. BARBOSA MS, 1990, EMBO J, V9, P153, DOI 10.1002/j.1460-2075.1990.tb08091.x
  7. Boccardo E, 2010, CARCINOGENESIS, V31, P521, DOI 10.1093/carcin/bgp333
  8. Cattani P, 1998, CLIN CANCER RES, V4, P2585
  9. Chowdhury D, 2006, MOL CELL, V23, P133, DOI 10.1016/j.molcel.2006.06.005
  10. CROOK T, 1991, CELL, V67, P547, DOI 10.1016/0092-8674(91)90529-8
  11. Doorbar J, 2005, J CLIN VIROL, V32, pS7, DOI 10.1016/j.jcv.2004.12.006
  12. Duensing S, 2000, P NATL ACAD SCI USA, V97, P10002, DOI 10.1073/pnas.170093297
  13. Duensing S, 2002, CANCER RES, V62, P7075
  14. DYSON N, 1989, SCIENCE, V243, P934, DOI 10.1126/science.2537532
  15. Francis DA, 2000, J VIROL, V74, P2679, DOI 10.1128/JVI.74.6.2679-2686.2000
  16. Gagne SE, 2005, JAIDS-J ACQ IMM DEF, V40, P182, DOI 10.1097/01.qai.0000179460.61987.33
  17. Hanahan D, 2011, CELL, V144, P646, DOI 10.1016/j.cell.2011.02.013
  18. Hasan M, 2013, NAT IMMUNOL, V14, P61, DOI 10.1038/ni.2475
  19. Kavanagh D, 2008, CELL CYCLE, V7, P1718, DOI 10.4161/cc.7.12.6162
  20. KESSIS TD, 1993, P NATL ACAD SCI USA, V90, P3988, DOI 10.1073/pnas.90.9.3988
  21. LECHNER MS, 1992, EMBO J, V11, P3045, DOI 10.1002/j.1460-2075.1992.tb05375.x
  22. Lembo D, 2006, VIRUS RES, V122, P189, DOI 10.1016/j.virusres.2006.06.011
  23. Lindahl T, 2009, BIOCHEM SOC T, V37, P535, DOI 10.1042/BST0370535
  24. Manawapat-Klopfer A, 2016, AM J CANCER RES, V6, P1524
  25. McMurray HR, 2001, INT J EXP PATHOL, V82, P15, DOI 10.1046/j.1365-2613.2001.00177.x
  26. Morita M, 2004, MOL CELL BIOL, V24, P6719, DOI 10.1128/mcb.247.15.6719-6727.2004
  27. MUNGER K, 1989, J VIROL, V63, P4417
  28. Nees M, 2001, J VIROL, V75, P4283, DOI 10.1128/JVI.75.9.4283-4296.2001
  29. Rao PH, 2004, BMC CANCER, V4, DOI 10.1186/1471-2407-4-5
  30. Rey O, 1999, ONCOGENE, V18, P6997, DOI 10.1038/sj.onc.1203180
  31. Ronco LV, 1998, GENE DEV, V12, P2061, DOI 10.1101/gad.12.13.2061
  32. SCHEFFNER M, 1990, CELL, V63, P1129, DOI 10.1016/0092-8674(90)90409-8
  33. Scotto L, 2008, GENE CHROMOSOME CANC, V47, P755, DOI 10.1002/gcc.20577
  34. Sherman L, 2002, VIROLOGY, V292, P309, DOI 10.1006/viro.2001.1263
  35. Shin KH, 2006, INT J ONCOL, V28, P209
  36. Sokolova I, 2007, J MOL DIAGN, V9, P604, DOI 10.2353/jmoldx.2007.070007
  37. Srivenugopal KS, 2002, ONCOGENE, V21, P5940, DOI 10.1038/sj.onc.1205762
  38. Steenbergen RDM, 1998, J VIROL, V72, P749
  39. STEENBERGEN RDM, 1995, CANCER RES, V55, P5465
  40. Therrien JP, 1999, P NATL ACAD SCI USA, V96, P15038, DOI 10.1073/pnas.96.26.15038
  41. Thomas JT, 1998, J VIROL, V72, P1131
  42. Wang CJ, 2009, DNA REPAIR, V8, P1179, DOI 10.1016/j.dnarep.2009.06.006
  43. Wilson R, 2016, NAT COMMUN, V7, DOI 10.1038/ncomms13597
  44. Wilting S, 2006, J PATHOL, V209, P220, DOI 10.1002/path.1966
  45. Wilting SM, 2009, BMC MED GENOMICS, V2, DOI 10.1186/1755-8794-2-32
  46. Wistuba II, 1997, CANCER RES, V57, P3154
  47. Yan N, 2010, NAT IMMUNOL, V11, P1005, DOI 10.1038/ni.1941
  48. Yang YG, 2007, CELL, V131, P873, DOI 10.1016/j.cell.2007.10.017
  49. Zhai Y, 2007, CANCER RES, V67, P10163, DOI 10.1158/0008-5472.CAN-07-2056