MicroRNA-24 is a novel regulator of aldosterone and cortisol production in the human adrenal cortex

Robertson, S., MacKenzie, S. M. , Alvarez-Madrazo, S., Diver, L. A., Lin, J., Stewart, P. M., Fraser, R., Connell, J. M. and Davies, E. (2013) MicroRNA-24 is a novel regulator of aldosterone and cortisol production in the human adrenal cortex. Hypertension, 62(3), pp. 572-578. (doi: 10.1161/HYPERTENSIONAHA.113.01102) (PMID:23836801)

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Abstract

Dysregulation of aldosterone or cortisol production can predispose to hypertension, as seen in aldosterone-producing adenoma, a form of primary aldosteronism. We investigated the role of microRNA (miRNA) in their production, with particular emphasis on the CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) genes, which produce the enzymes responsible for the final stages of cortisol and aldosterone biosynthesis, respectively. Knockdown of Dicer1, a key enzyme in miRNA maturation, significantly altered CYP11B1 and CYP11B2 expression in a human adrenocortical cell line. Screening of nondiseased human adrenal and aldosterone-producing adenoma samples yielded reproducible but distinctive miRNA expression signatures for each tissue type, with levels of certain miRNA, including microRNA-24 (miR-24), differing significantly between the 2. Bioinformatic analysis identified putative binding sites for several miRNA, including miR-24, in the 3′ untranslated region of CYP11B1 and CYP11B2 mRNAs. In vitro manipulation of miR-24 confirmed its ability to modulate CYP11B1 and CYP11B2 expression, as well as cortisol and aldosterone production. This study demonstrates that Dicer-dependent miRNA, including miR-24, can post-transcriptionally regulate expression of the CYP11B1 and CYP11B2 genes. Normal adrenal tissue and aldosterone-producing adenoma differ significantly and reproducibly in their miRNA expression profiles, with miR-24 significantly downregulated in the latter. Adrenal miRNA may, therefore, be a novel and valid target for the therapeutic manipulation of corticosteroid biosynthesis.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Davies, Professor Eleanor and Stewart, Prof Paul and Connell, Professor John and MacKenzie, Dr Scott and Fraser, Prof Robert and Lin, Mr Junjun and Diver, Miss Louise and Robertson, Dr Stacy and Alvarez-Madrazo, Dr Samantha
Authors: Robertson, S., MacKenzie, S. M., Alvarez-Madrazo, S., Diver, L. A., Lin, J., Stewart, P. M., Fraser, R., Connell, J. M., and Davies, E.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Hypertension
Publisher:Lippincott Williams & Wilkins
ISSN:0194-911X
ISSN (Online):1524-4563
Published Online:08 July 2013

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
486601Regulation of aldosterone synthase (CYP11B2) and 11b-Hydroxylase gene expression by novel micro RNAsEleanor DaviesBritish Heart Foundation (BHF)PG/09/092/28075RI CARDIOVASCULAR & MEDICAL SCIENCES