Micrornas In Prostate Cancer: Implications For Personalized Medicine.

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Abstract

Introduction: There is a clinical need for biomarkers that can help develop personalized medicine for prostate cancer. MicroRNAs (miRNAs) are small, non-coding RNA species which regulate gene expression by interacting with messenger RNAs (mRNAs). miRNAs are attractive candidates as biomarkers, since they are stably preserved in clinical samples, including FFPE tissues, serum and urine, and can be readily detected by PCR. In this study we highlight the potential of various miRNAs as biomarkers in prostate cancer.Methods: microRNAs of interest were selected by bioinformatics analyses performed on prostate cancer biopsy datasets held in The Cancer Genome Atlas (TCGA) repository. Expression of selected miRNAs (miR-205, miR-200c, miR-141, miR-24 and miR-210) were subsequently profiled by PCR in a panel of prostate cancer cell-lines and in a small cohort of clinical prostate biopsy specimens. Functional analysis, identification of targets and correlation with clinicopathological parameters were performed by in vitro bioassays and further in silico analysis. Result: TCGA analysis revealed several miRNAs that were significantly correlated with clinicopathological parameters (Gleason, TNM staging, PSA). Of these, we progressed to show in vitro that miR-210 is induced by hypoxia, an important factor in prostate cancer progression. In a small pilot dataset, we found miR-24 was down-regulated in tumour tissue compared to matched normal tissue. miR-200c and miR-141 displayed variable expression in these clinical samples, dependent on the methylation status of their shared promoter. mRNA targets and functional networks of each selected miRNA were identified, revealing the complex network of interactions that determine their functionality in prostate cancer. Discussion: In this study, we provide representative examples to illustrate that miRNAs play an important role in the pathogenesis of prostate cancer.Increasing our understanding of the functionality of specific miRNAs in prostate cancer will be instrumental in developing this exciting field of research so that it can inform precision medicine and improve patient outcome.
Original languageEnglish
Title of host publicationUnknown Host Publication
PublisherC-TRIC
Number of pages40
Publication statusAccepted/In press - 7 Sep 2017
EventC-TRIC 8th Annual Translational Medicine Conference - City Hotel, Derry
Duration: 7 Sep 2017 → …

Conference

ConferenceC-TRIC 8th Annual Translational Medicine Conference
Period7/09/17 → …

Keywords

  • MicroRNas
  • prostate cancer

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  • Cite this

    angel, Z., Lynch, S., Walsh, CP., & McKenna, D. (Accepted/In press). Micrornas In Prostate Cancer: Implications For Personalized Medicine. In Unknown Host Publication C-TRIC.