Downregulation of miR‐375 in aldosterone‐producing adenomas promotes tumour cell growth via MTDH

摘要: SummaryObjective Previous studies have investigated the genetic and molecular basis of primary aldosteronism (PA), a common cause human hypertension, but effects microRNAs (miRNAs) on adrenocortical cell proliferation aldosterone production are largely obscure. Here, we characterized miRNA expression patterns in subtypes PA to gain better understanding its pathogenesis. Methods miRNA was assessed by microarray profiling analysis aldosterone-producing adenoma (APA), unilateral adrenal hyperplasia (UAH) normal cortex tissues. Selected differentially expressed miRNAs were further validated validation cohort qRT-PCR. A gain-of-function approach used explore functional role specific in vitro. Results Of 31 including miR-375, miR-7 miR-29b found be significantly among these three groups. miR-375 most downregulated one tissues from patients, level inversely correlated with tumour size APA. Overexpression line (H295R) reduced suppressed MTDH (metadherin, also known as astrocyte elevated gene-1). Moreover, verified direct target through luciferase reporter assays. Knock-down H295R cells attenuated Akt-Ser473 phosphorylation inhibited viability. Conclusion Our findings suggest that exerts tumour-suppressive function via targeting MTDH/Akt pathway implicate potential therapeutic PA.