Regulation of miR200c and miR141 by methylation in prostate cancer

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

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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
Title of host publicationUnknown Host Publication
PublisherIrish Association for Cancer Research
Number of pages1
Publication statusAccepted/In press - 22 Feb 2017
EventIrish Association for Cancer Research 2017 - Kilkenny, Ireland
Duration: 22 Feb 2017 → …

Conference

ConferenceIrish Association for Cancer Research 2017
Period22/02/17 → …

Keywords

  • miR-200c
  • miR-141
  • prostate cancer
  • mehtlyation

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    Lynch, S., O'Neill, K., McKenna, M., Walsh, CP., & McKenna, D. (Accepted/In press). Regulation of miR200c and miR141 by methylation in prostate cancer. In Unknown Host Publication Irish Association for Cancer Research.