Comprehensive Study of Gene and microRNA Expression Related to Epithelial-Mesenchymal Transition in Prostate Cancer

Carregando...
Imagem de Miniatura
Citações na Scopus
38
Tipo de produção
article
Data de publicação
2014
Título da Revista
ISSN da Revista
Título do Volume
Editora
PUBLIC LIBRARY SCIENCE
Citação
PLOS ONE, v.9, n.11, article ID e113700, 10p, 2014
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Prostate cancer is the most common cancer in men, and most patients have localized disease at the time of diagnosis. However, 4% already present with metastatic disease. Epithelial-mesenchymal transition is a fundamental process in carcinogenesis that has been shown to be involved in prostate cancer progression. The main event in epithelial-mesenchymal transition is the repression of E-cadherin by transcription factors, but the process is also regulated by microRNAs. The aim of this study was to analyze gene and microRNA expression involved in epithelial-mesenchymal transition in localized prostate cancer and metastatic prostate cancer cell lines and correlate with clinicopathological findings. We studied 51 fresh frozen tissue samples from patients with localized prostate cancer (PCa) treated by radical prostatectomy and three metastatic prostate cancer cell lines (LNCaP, DU145, PC3). The expression of 10 genes and 18 miRNAs were assessed by real-time PCR. The patients were divided into groups according to Gleason score, pathological stage, preoperative PSA, biochemical recurrence, and risk group for correlation with clinicopathological findings. The majority of localized PCa cases showed an epithelial phenotype, with overexpression of E-cadherin and underexpression of the mesenchymal markers. MiRNA-200 family members and miRNAs 203, 205, 183, 373, and 21 were overexpressed, while miRNAs 9, 495, 29b, and 1 were underexpressed. Low-expression levels of miRNAs 200b, 30a, and 1 were significantly associated with pathological stage. Lower expression of miR-200b was also associated with a Gleason score >= 8 and shorter biochemical recurrence-free survival. Furthermore, low-expression levels of miR-30a and high-expression levels of Vimentin and Twist1 were observed in the high-risk group. Compared with the primary tumor, the metastatic cell lines showed significantly higher expression levels of miR-183 and Twist1. In summary, miRNAs 200b, 30a, 1, and 183 and the genes Twist1 and Vimentin might play important roles in the progression of prostate cancer and may eventually become important prognostic markers.
Palavras-chave
Referências
  1. Ambs S, 2008, CANCER RES, V68, P6162, DOI 10.1158/0008-5472.CAN-08-0144
  2. Barron N, 2012, PROSTATE, V72, P1193, DOI 10.1002/pros.22469
  3. Bartel DP, 2004, CELL, V116, P281, DOI 10.1016/S0092-8674(04)00045-5
  4. Batlle E, 2000, NAT CELL BIOL, V2, P84, DOI 10.1038/35000034
  5. Behnsawy HM, 2013, BJU INT, V111, P30, DOI 10.1111/j.1464-410X.2012.11551.x
  6. Bendoraite A, 2010, GYNECOL ONCOL, V116, P117, DOI 10.1016/j.ygyno.2009.08.009
  7. Bethel CR, 2006, CANCER RES, V66, P10683, DOI 10.1158/0008-5472.CAN-06-0963
  8. Bracken CP, 2008, CANCER RES, V68, P7846, DOI 10.1158/0008-5472.CAN-08-1942
  9. Burk U, 2008, EMBO REP, V9, P582, DOI 10.1038/embor.2008.74
  10. Carlsson J, 2011, CANCER CELL INT, V11, DOI 10.1186/1475-2867-11-14
  11. Casas E, 2011, CANCER RES, V71, P245, DOI 10.1158/0008-5472.CAN-10-2330
  12. Cheng CW, 2012, BREAST CANCER RES TR, V134, P1081, DOI 10.1007/s10549-012-2034-4
  13. Ding ZH, 2011, NATURE, V470, P269, DOI 10.1038/nature09677
  14. Eide T, 2013, CANCER CELL INT, V13, DOI 10.1186/1475-2867-13-4
  15. Epstein JI, 2005, AM J SURG PATHOL, V29, P1228, DOI 10.1097/01.pas.0000173646.99337.b1
  16. Graham TR, 2008, CANCER RES, V68, P2479, DOI 10.1158/0008-5472.CAN-07-2559
  17. Gregory PA, 2008, NAT CELL BIOL, V10, P593, DOI 10.1038/ncb1722
  18. Halbleib JM, 2006, GENE DEV, V20, P3199, DOI 10.1101/gad.1486806
  19. Hu XX, 2009, GYNECOL ONCOL, V114, P457, DOI 10.1016/j.ygyno.2009.05.022
  20. Huber MA, 2005, CURR OPIN CELL BIOL, V17, P548, DOI 10.1016/j.ceb.2005.08.001
  21. Hudson RS, 2012, NUCLEIC ACIDS RES, V40, P3689, DOI 10.1093/nar/gkr1222
  22. Iwata T, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0009427
  23. Kao CJ, 2013, ONCOGENE
  24. Kojima S, 2012, BRIT J CANCER, V106, P405, DOI 10.1038/bjc.2011.462
  25. Kong DJ, 2009, STEM CELLS, V27, P1712, DOI 10.1002/stem.101
  26. Korpal M, 2008, J BIOL CHEM, V283, P14910, DOI 10.1074/jbc.C800074200
  27. Kumarswamy R, 2012, INT J CANCER, V130, P2044, DOI 10.1002/ijc.26218
  28. Kurashige J, 2012, ANN SURG ONCOL, V19, pS656, DOI 10.1245/s10434-012-2217-6
  29. Kwok WK, 2005, CANCER RES, V65, P5153, DOI 10.1158/0008-5472.CAN-04-3785
  30. Li XL, 2014, MOL CELL BIOL, V34, P533, DOI 10.1128/MCB.01043-13
  31. Liu Y, 2012, MED SCI MONITOR, V18, pBR299
  32. Liu YN, 2008, MOL CELL BIOL, V28, P7096, DOI 10.1128/MCB.00449-08
  33. Liu YN, 2013, ONCOGENE, V32, P296, DOI 10.1038/onc.2012.58
  34. Ma L, 2007, NATURE, V449, P682, DOI 10.1038/nature06174
  35. Mackinnon AC, 2009, ARCH PATHOL LAB MED, V133, P1033, DOI 10.1043/1543-2165-133.7.1033
  36. Marchini S, 2011, LANCET ONCOL, V12, P273, DOI 10.1016/S1470-2045(11)70012-2
  37. Moreno-Bueno G, 2006, CANCER RES, V66, P9543, DOI 10.1158/0008-5472.CAN-06-0479
  38. Nam EJ, 2008, CLIN CANCER RES, V14, P2690, DOI 10.1158/1078-0432.CCR-07-1731
  39. Park SM, 2008, GENE DEV, V22, P894, DOI 10.1101/gad.1640608
  40. Paterson EL, 2008, THESCIENTIFICWORLDJO, V8, P901, DOI 10.1100/tsw.2008.115
  41. Porkka KP, 2007, CANCER RES, V67, P6130, DOI 10.1158/0008-5472.CAN-07-0533
  42. Putzke AP, 2011, AM J PATHOL, V179, P400, DOI 10.1016/j.ajpath.2011.03.028
  43. Qu Y, 2013, INT J CANCER, V133, P544, DOI 10.1002/ijc.28056
  44. Quinn DI, 2001, J CLIN ONCOL, V19, P3692
  45. Ru P, 2012, MOL CANCER THER, V11, P1166, DOI 10.1158/1535-7163.MCT-12-0100
  46. Sarver AL, 2010, CANCER RES, V70, P9570, DOI 10.1158/0008-5472.CAN-10-2074
  47. Siegel R, 2013, CA-CANCER J CLIN, V63, P11, DOI 10.3322/caac.21166
  48. Siemens H, 2011, CELL CYCLE, V10, P4256, DOI 10.4161/cc.10.24.18552
  49. Sun YT, 2012, CANCER RES, V72, P527, DOI 10.1158/0008-5472.CAN-11-3004
  50. Taylor BS, 2010, CANCER CELL, V18, P11, DOI 10.1016/j.ccr.2010.05.026
  51. Thiery JP, 2009, CELL, V139, P871, DOI 10.1016/j.cell.2009.11.007
  52. Tomita K, 2000, CANCER RES, V60, P3650
  53. Ueno K, 2013, BRIT J CANCER, V108, P1659, DOI 10.1038/bjc.2013.125
  54. Vernon AE, 2004, CURR BIOL, V14, pR719, DOI 10.1016/j.cub.2004.08.048
  55. Wang W, 2013, EUR J SURG ONCOL
  56. Weeraratne SD, 2012, ACTA NEUROPATHOL, V123, P539, DOI 10.1007/s00401-012-0969-5
  57. Wellner U, 2009, NAT CELL BIOL, V11, P1487, DOI 10.1038/ncb1998
  58. Williams LV, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0083991
  59. Xu G, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0015519
  60. Yang J, 2004, CELL, V117, P927, DOI 10.1016/j.cell.2004.06.006
  61. Yuen HF, 2007, HISTOPATHOLOGY, V50, P648, DOI 10.1111/j.1365-2559.2007.02665.x
  62. Zhang JC, 2012, BIOCHEM BIOPH RES CO, V417, P1100, DOI 10.1016/j.bbrc.2011.12.121
  63. Zhu ML, 2010, FASEB J, V24, P769, DOI 10.1096/fj.09-136994