Investigating the role of microRNAs in the hypoxic response in prostate cancer

Zoe Angel, Seodhna M Lynch, Heather Nesbitt, CP Walsh, Declan J McKenna

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Introduction: Hypoxia (a pathologically low oxygen level) is a well-established driver of aggressive behaviour in
prostate cancer (PCa). However, the reasons for this are not completely characterised and the role of microRNAs
(miRNAs) in the hypoxic response remains unclear. In this study we investigate the expression and functional role of
miRNAs in response to hypoxia in prostate cancer.
Methods: Three models of PCa hypoxia were utilised (i) in vitro culture at 0.1% oxygen (ii) 3D spheroid culture and
(iii) an in vivo tumour xenograft experiment. miRNA expression was measured by RT-qPCR. miRNA overexpression
was achieved by transfection and the effect on selected targets was assessed by RT-qPCR and Western blots. Cell
proliferation, apoptosis, migration and invasion abilities were assessed by functional bioassays. miRNA-seq and
mRNA-seq was used to examine expression patterns in a small cohort of prostate biopsies. Bionformatic analysis of
prostate cancer data in The Cancer Genome Atlas (TCGA) repository was also performed.
Results: Several miRNAs were identified as being affected by hypoxia in prostate cells. Among these, miR-210 and
miR-21 were shown to be upregulated by hypoxia in our various models. The subsequent effect on their respective
networks of target genes was explored and we demonstrate for the first time that miR-210 targets neural cell
adhesion molecule (NCAM) in prostate cells. miR-210 and miR-21 expression was positively correlated with markers
of hypoxia and tumour aggressiveness in clinical samples, suggesting they may have value as novel biomarkers in this
Discussion: We provide evidence that various miRNAs can contribute to the progression of PCa through
hypoxia-related mechanisms. In particular, miR-210 and miR-21 appear to play key roles in the hypoxic response
which can contribute to PCa progression. We propose that miRNA profiling of these and other miRNAs has great
value for improving diagnostic, prognostic and potential therapeutic approaches in this disease.
Original languageEnglish
Title of host publicationKeystone Symposia Conference D7: Small Regulatory RNAs Conference Programme
Publication statusPublished (in print/issue) - 2019
EventKeystone Symposia Conference D7: Small Regulatory RNAs - Daejeon Convention Center, Daejon, Korea, Republic of
Duration: 14 Apr 201918 Jun 2019


ConferenceKeystone Symposia Conference D7: Small Regulatory RNAs
Country/TerritoryKorea, Republic of
Internet address


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