The Significance of High Expression of Circulating miR-222-3p in Patients With Unilateral Primary Aldosteronism

CONTEXT: The significance of circulating microRNAs (miRNAs) in primary aldosteronism (PA) is still largely unknown. OBJECTIVE: We compared the profiles of circulating miRNAs between unilateral primary aldosteronism (UPA) and bilateral hyperaldosteronism (BHA) and investigated the potential role of a newly identified UPA-related miRNA in the pathogenesis of PA. METHODS: We initially conducted a comprehensive expression analysis of circulating miRNAs using a quantitative polymerase chain reaction panel in a small number of cases matched for background factors, followed by validation analysis with a larger sample size for the candidate miRNAs. RESULTS: The expression level of one single miRNA, miR-222-3p, was significantly higher in UPA than in BHA, both in the adrenal veins and the inferior vena cava. Moreover, it was significantly higher in the adrenal vein on the tumor side compared to the nontumor side within the same UPA patients. In primary cultured adrenal cells, miR-222-3p mimics appeared to increase CYP11B2 expression, although the effect was not statistically significant. However, transfection with miR-222-3p mimics significantly increased cell proliferation, whereas transfection with miR-222-3p inhibitors decreased it. CDKN1B was identified as a predicted target gene of miR-222-3p. Additionally, the expression level of miR-222-3p exhibited a significant positive correlation with tumor diameter and plasma aldosterone concentration after saline infusion test. CONCLUSION: The present results demonstrated higher expression of circulating miR-222-3p in UPA than in BHA, providing a biochemical marker for subtype diagnosis of PA. Moreover, the correlation of miR-222-3p with adrenal cell proliferation and aldosterone secretion indicated its significant involvement in the pathogenesis of PA.