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 > School of Cardiovascular & Metabolic Health 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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