MicroRNA-24 Is a Novel Regulator of Aldosterone and Cortisol Production in the Human Adrenal Cortex

<jats:p> 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 <jats:italic>CYP11B1</jats:italic> (11β-hydroxylase) and <jats:italic>CYP11B2</jats:italic> (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 <jats:italic>CYP11B1</jats:italic> and <jats:italic>CYP11B2</jats:italic> 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 <jats:italic>CYP11B1</jats:italic> and <jats:italic>CYP11B2</jats:italic> mRNAs. In vitro manipulation of miR-24 confirmed its ability to modulate <jats:italic>CYP11B1</jats:italic> and <jats:italic>CYP11B2</jats:italic> 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 <jats:italic>CYP11B1</jats:italic> and <jats:italic>CYP11B2</jats:italic> 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. </jats:p>