Regulation of CYP11B1 and CYP11B2 steroidogenic genes by hypoxia-inducible miR-10b in H295R cells.

Abstract

Although numerous studies have shown that hypoxia affects cortisol and aldosterone production in vivo, the underlying molecular mechanisms regulating the steroidogenic genes of these steroid hormones are still poorly known. MicroRNAs are post-transcriptional regulators that control diverse biological processes and this study describes the identification and validation of the hypoxia-inducible microRNA, miR-10b, as a negative regulator of the CYP11B1 and CYP11B2 steroidogenic genes in H295R human adrenocortical cells. Using the human TaqMan Low Density miRNA Arrays, we determined the miRNA expression patterns in H295R cells under normoxic and hypoxic conditions, and in cells overexpressing the human HIF-1α. Computer analysis using three in silico algorithms predicted that the hypoxia-inducible miR-10b molecule targets CYP11B1 and CYP11B2 mRNAs. Gene transfection studies of luciferase constructs containing the 3'-untranslated region of CYP11B1 or CYP11B2, combined with miRNA overexpression and knockdown experiments provide compelling evidence that CYP11B1 and CYP11B2 mRNAs are likely targets of miR-10b.

• Authors: Suraia Nusrin, Steve K H Tong, G Chaturvedi, Rudolf S S Wu, John P Giesy, Richard Y C Kong
• Journal: Marine pollution bulletin (Mar Pollut Bull) Vol. 85 Issue 2 Pg. 344-51 (Aug 30 2014) ISSN: 1879-3363 [Electronic] England
• PMID: 24768260 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• MIRN10 microRNA, human
• MicroRNAs
• RNA, Messenger
• Aldosterone
• Cytochrome P-450 CYP11B2
• Steroid 11-beta-Hydroxylase
• Hydrocortisone

Topics

• Aldosterone (metabolism)
• Cell Hypoxia
• Cell Line
• Computer Simulation
• Cytochrome P-450 CYP11B2 (genetics)
• Gene Expression Regulation
• Gene Knockdown Techniques
• Humans
• Hydrocortisone (metabolism)
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics, metabolism)
• MicroRNAs (genetics, metabolism, physiology)
• RNA, Messenger (metabolism)
• Steroid 11-beta-Hydroxylase (genetics)