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Clin Epigenetics. 2015 Apr 10;7:42. doi: 10.1186/s13148-015-0076-2. eCollection 2015.

MicroRNA-375 plays a dual role in prostate carcinogenesis.

Clinical epigenetics

Pedro Costa-Pinheiro, João Ramalho-Carvalho, Filipa Quintela Vieira, Jorge Torres-Ferreira, Jorge Oliveira, Céline S Gonçalves, Bruno M Costa, Rui Henrique, Carmen Jerónimo

Affiliations

  1. Cancer Biology and Epigenetics Group - Research Center (Lab3), Portuguese Oncology Institute - Porto (IPO-Porto), Rua Dr. António Bernardino de Almeida, Porto, 4200-072 Portugal.
  2. School of Allied Health Sciences (ESTSP), Polytechnic of Porto, Rua Valente Perfeito 322, Vila Nova de Gaia, 4400-330 Portugal.
  3. Department of Urology, Portuguese Oncology Institute, Rua Dr. António Bernardino de Almeida, Porto, 4200-072 Portugal.
  4. Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Rua da Universidade, 4704-553 Braga, Portugal.
  5. ICVS/3B's - PT Government Associate Laboratory, Universidade do Minho, Campus de Gualtar, 4710-057 Guimarães, Braga Portugal.
  6. Department of Pathology, Portuguese Oncology Institute - Porto, Rua Dr. António Bernardino de Almeida, Porto, 4200-072 Portugal.
  7. Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, Porto, 4050-313 Portugal.

PMID: 25977730 PMCID: PMC4431534 DOI: 10.1186/s13148-015-0076-2

Abstract

BACKGROUND: Prostate cancer (PCa), a highly incident and heterogeneous malignancy, mostly affects men from developed countries. Increased knowledge of the biological mechanisms underlying PCa onset and progression are critical for improved clinical management. MicroRNAs (miRNAs) deregulation is common in human cancers, and understanding how it impacts in PCa is of major importance. MiRNAs are mostly downregulated in cancer, although some are overexpressed, playing a critical role in tumor initiation and progression. We aimed to identify miRNAs overexpressed in PCa and subsequently determine its impact in tumorigenesis.

RESULTS: MicroRNA expression profiling in primary PCa and morphological normal prostate (MNPT) tissues identified 17 miRNAs significantly overexpressed in PCa. Expression of three miRNAs, not previously associated with PCa, was subsequently assessed in large independent sets of primary tumors, in which miR-182 and miR-375 were validated, but not miR-32. Significantly higher expression levels of miR-375 were depicted in patients with higher Gleason score and more advanced pathological stage, as well as with regional lymph nodes metastases. Forced expression of miR-375 in PC-3 cells, which display the lowest miR-375 levels among PCa cell lines, increased apoptosis and reduced invasion ability and cell viability. Intriguingly, in 22Rv1 cells, which displayed the highest miR-375 expression, knockdown experiments also attenuated the malignant phenotype. Gene ontology analysis implicated miR-375 in several key pathways deregulated in PCa, including cell cycle and cell differentiation. Moreover, CCND2 was identified as putative miR-375 target in PCa, confirmed by luciferase assay.

CONCLUSIONS: A dual role for miR-375 in prostate cancer progression is suggested, highlighting the importance of cellular context on microRNA targeting.

Keywords: CCND2; Epigenetics; MicroRNAs; Prostate cancer; miR-375

References

  1. PLoS One. 2013 Jul 30;8(7):e69239 - PubMed
  2. Nature. 2000 Jun 15;405(6788):827-36 - PubMed
  3. Genes Dev. 2010 Sep 15;24(18):1967-2000 - PubMed
  4. Int J Cancer. 2012 Feb 1;130(3):611-21 - PubMed
  5. Int J Cancer. 2012 Aug 1;131(3):652-61 - PubMed
  6. Genes Chromosomes Cancer. 2008 Jul;47(7):565-72 - PubMed
  7. Eur J Cancer. 2013 Apr;49(6):1374-403 - PubMed
  8. Prostate. 2013 Jun;73(8):827-34 - PubMed
  9. Eur Urol. 2011 Oct;60(4):753-66 - PubMed
  10. Endocr Relat Cancer. 2010 Jan 29;17(1):F1-17 - PubMed
  11. Cancer Res. 2010 Mar 15;70(6):2339-49 - PubMed
  12. Nucleic Acids Res. 2014 Jan;42(Database issue):D68-73 - PubMed
  13. Clin Cancer Res. 2009 Apr 15;15(8):2850-5 - PubMed
  14. Bioinformatics. 2009 Jan 15;25(2):288-9 - PubMed
  15. Nat Protoc. 2008;3(6):1101-8 - PubMed
  16. J Clin Oncol. 2009 Dec 1;27(34):5848-56 - PubMed
  17. Cell Res. 2010 Jul;20(7):784-93 - PubMed
  18. BMC Genomics. 2009 Feb 26;10:93 - PubMed
  19. Biochem Biophys Res Commun. 2009 Sep 11;387(1):196-201 - PubMed
  20. Nat Rev Genet. 2009 Oct;10(10):704-14 - PubMed
  21. Bioinformatics. 2004 Dec 12;20(18):3710-5 - PubMed
  22. Dis Markers. 2007;23(1-2):31-41 - PubMed
  23. EMBO Mol Med. 2012 Mar;4(3):143-59 - PubMed
  24. Eur Urol. 2011 May;59(5):671-81 - PubMed
  25. Cell Cycle. 2014;13(2):227-39 - PubMed
  26. Hepatology. 2008 Jun;47(6):1955-63 - PubMed
  27. Mol Cell. 2014 Mar 20;53(6):1031-43 - PubMed
  28. Oncol Rep. 2014 Jan;31(1):34-40 - PubMed
  29. Cancer Res. 2007 Jul 1;67(13):6130-5 - PubMed
  30. Curr Opin Oncol. 2010 Jan;22(1):35-45 - PubMed
  31. Eur Urol. 2015 Jan;67(1):33-41 - PubMed
  32. Prostate. 2013 Mar;73(4):346-54 - PubMed
  33. CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29 - PubMed
  34. Nat Rev Drug Discov. 2012 Nov;11(11):860-72 - PubMed
  35. Mol Cancer Res. 2011 Jun;9(6):791-800 - PubMed
  36. Oncogene. 2007 Jun 28;26(30):4442-52 - PubMed
  37. PLoS Genet. 2013;9(3):e1003311 - PubMed

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