tsRNA-25172 inhibits aldosterone secretion in aldosterone-producing adenomas

The pathophysiology of aldosterone-producing adenomas (APAs) is characterized by aldosterone hypersecretion. Transfer RNA-derived small RNAs (tsRNAs) are novel non-coding RNAs, which are involved in multiple biological processes. However, the role of tsRNAs in aldosterone synthesis and APAs remains poorly understood. Herein, immunohistochemistry was employed to assess the expression levels of aldosterone synthase CYP11B2 in APA patients. The differentially expressed miRNAs, piRNAs, and tsRNAs between adrenocortical adenomas (ACAs) and normal tissues were identified using small RNA sequencing data. The regulatory role of tsRNA-25172 on aldosterone synthesis in NCI-H295R cells was evaluated by qRT-PCR, CCK-8, and ELISA. We observed an abnormal increase in CYP11B2 expression in APA tissues. A total of 18 differentially expressed miRNAs, 5 differentially expressed piRNAs, and 159 differentially expressed tsRNAs were identified between ACA and normal tissues. Enrichment analysis revealed that dysregulated small RNAs were predominantly associated with cell adhesion, intracellular signal transduction, calcium signaling, and Wnt signaling pathways, leading to the identification of an ER-related gene, TGM2. tsRNA-25172 and tsRNA-25173 were downregulated in the ACA group. tsRNA-25172 mimics significantly inhibited the levels of aldosterone and cortisol in NCI-H295R cells. In contrast, tsRNA-25173 did not exhibit a notable effect. Moreover, overexpressed tsRNA-25172 markedly inhibited CYP11B2 and its target gene TGM2. Our findings reveal a pivotal role for tsRNA in APAs, potentially offering a novel exploratory approach and therapeutic target for the pathogenesis of APAs.