Differentially expressed miRNAs in zona reticularis cells of the human adrenal cortex

FRANCISCO GARCÍA, DIEGO COLMAN, LUCIANA ZOFF, NORA SARACO, ALICIA BELGOROSKY, MARÍA SONIA BAQUEDANO

Congreso; SAIC 2019; 2019

The human adrenal cortex, involved in adaptive responses to stress, fluid homeostasis,and secondary sexual characteristics, arises from a tightly regulated development of azone and cell type-specific secretory pattern. However, the molecular mechanismsgoverning adrenal zonation, particularly postnatal ZR development, which producesadrenal androgens in a life-time-specific manner, remain poorly understood. Thehallmark of ZR is the low expression of type 2 3β-hydroxysteroid dehydrogenase(HSD3B2). However, the mechanisms underlying HSD3B2 downregulation in the ZRremain unknown. MiRNAs are seen as regulators of cell phenotypes.The objective of the study was to compare miRNA expression profiles in humanadrenal ZR and zona fasciculata (ZF).ZF and ZR were microdissected from 5 human adrenals tissues by laser capturemicrodissection (LCM). Total RNA was extracted from 5 ZF/ZR pairs and nextgenerationsequencing (NGS) was used to perform the microRNA expression profiling.281 mature microRNAs were identified in human adrenal cortex. Among them, 7microRNAs were significantly differentially expressed between ZF and ZR. Theexpression of miR-375-3p, miR-483-3p and miR-7-5p was higher in ZR compared withits paired ZF by 2-fold or greater. Multiple available bioinformatic algorithms(TargetScan, miRanda, DianaLab and PicTar) were employed to search for its targetgenes. Among predicted target genes, several genes (GATA-6, GATA-4, SF1, NR4A2,and IGF-1) are known to be involved in HSD3B2 regulation. In summary, LCMcombined with NGS provided a robust approach to explore the adrenal zone-specificmicro-RNA profiling. Our data gave first hints that miRNAs might be novel regulatorymodules associated with human adrenal ZR cell-specific transcript regulationunderlying developmental androgen production.