Androgen-regulated processing of the oncomir miR-27a, which targets Prohibitin in prostate cancer.

Abstract

MicroRNAs (miRs) play an important role in the development of many complex human diseases and may have tumour suppressor or oncogenic (oncomir) properties. Prostate cancer is initially an androgen-driven disease, and androgen receptor (AR) remains a key driver of growth even in castration-resistant tumours. However, AR-mediated oncomiR pathways remain to be elucidated. We demonstrate that miR-27a is an androgen-regulated oncomir in prostate cancer, acting via targeting the tumour suppressor and AR corepressor, Prohibitin (PHB). Increasing miR-27a expression results in reduced PHB mRNA and protein levels, and increased expression of AR target genes and prostate cancer cell growth. This involves a novel mechanism for androgen-mediated miR regulation, whereby AR induces a transient increase in miR-23a27a24-2 transcription, but more significantly accelerates processing of the primiR-23a27a24-2 cluster. Androgens therefore regulate miR-27a expression both transcriptionally (via AR binding to the cluster promoter) and post-transcriptionally (accelerating primiR processing to the mature form). We further show that a miR-27a anti-sense oligonucleotide, by opposing the effects of mir-27a, has therapeutic potential in prostate cancer.

DOI: 10.1093/hmg/dds139

6 Figures and Tables

0100200300201220132014201520162017
Citations per Year

541 Citations

Semantic Scholar estimates that this publication has 541 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Fletcher2012AndrogenregulatedPO, title={Androgen-regulated processing of the oncomir miR-27a, which targets Prohibitin in prostate cancer.}, author={Claire E. Fletcher and Dafydd Alwyn Dart and Ailsa Sita-Lumsden and Helen Cheng and Paul S. Rennie and Charlotte L. Bevan}, journal={Human molecular genetics}, year={2012}, volume={21 14}, pages={3112-27} }