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

Fletcher, Claire E., Dart, Dafydd Alwyn, Sita-Lumsden, Ailsa, Cheng, Helen, Rennie, Paul S. and Bevan, Charlotte L. 2012. Androgen-regulated processing of the oncomir MiR-27a, which targets Prohibitin in prostate cancer. Human Molecular Genetics 21 (14) , pp. 3112-3127. 10.1093/hmg/dds139

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher:	Oxford University Press
ISSN:	0964-6906
Last Modified:	08 Jan 2020 03:30
URI:	https://orca.cardiff.ac.uk/id/eprint/50290

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