Regulation of miR-200c and miR-141 by methylation in prostate cancer.

Seodhna Lynch, Karla O'Neill, Michael McKenna, Colum Walsh, Declan McKenna

Research output: Contribution to journalArticle

Abstract

Background: In prostate cancer (PCa), abnormal expression of several microRNAs (miRNAs) has been previously reported. Increasing evidence shows that aberrant epigenetic regulation is a contributing factor to their altered expression in cancer. In this study we investigate whether expression of miR-200c and miR-141 in PCa is related to the DNA methylation status of their promoter. Methods: PCR analysis of miR-200c and miR-141, and CpG methylation analysis of their common promoter, was performed in PCa cell-lines and in FFPE prostate biopsy specimens. The functionality of miR-200c and miR-141 expression in prostate cancer cells was assessed by a series of in vitro bioassays.Results: miR-200c and miR-141 expression correlates inversely with the methylation status of the miR-200c/miR-141 promoter in PCa cells. In PC3 cells, miR-200c and miR-141 expression is elevated by treatment with the demethylating agents suggesting their expression is linked to methylation. Expression of miR-200c and miR-141 in prostate biopsy tissue was inversely correlated with methylation in CpG sites closest to the miR-200c/miR-141 loci. Over-expression of miR-200c in PC3 cells inhibited growth and clonogenic potential, as well as inducing apoptosis. Expression of the genes DNMT3A and TET1/TET3 were down-regulated by miR-200c and miR-141 respectively. Finally, treatment with the soy isoflavone genistein caused demethylation of the promoter CpG sites closest to the miR-200c/miR-141 loci resulting in increased miR-200c expression.Conclusions: Our findings provide evidence that miR-200c and miR-141 are under epigenetic regulation in PCa cells. Profiling their expression and methylation status may have potential in the improved diagnosis and prognosis of PCa.
Original languageEnglish
Pages (from-to)11-12
JournalUlster Medical Journal, The
Volume87
Issue number1
Publication statusAccepted/In press - 9 Sep 2016

Keywords

  • miR-200c
  • miR-141
  • Prostate cancer
  • microRNA
  • methylaition
  • LNCaP
  • PC3

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