MicroRNA mediated downregulation of HSD17B1 impairs estrone-to-estradiol conversion in polycystic ovarian syndrome

Abstract

Polycystic ovary syndrome (PCOS) is a complicated disorder with genetic and epigenetic factors as the potential contributors of disease progression. The major findings of PCOS involves an imbalanced estrogen and androgen. The gene HSD17B1 is known to be involved in the synthesis of these steroids. Because miRNAs, which are short non-coding RNAs that regulate genes, are promising therapeutic possibilities for disease regulation, this study focused on the effect of miRNAs that target the HSD17B1 gene in PCOS. TargetScan database was used to identify the target miRNAs of HSD171B1. In-silico approaches were employed for prediction of expression levels of HSD17B1, miR-4430 and miR-200b-5p in PCOS and for the functional annotations of miRNAs. Validated the relative expression of HSD17B1, miR-4430, miR-200b-5p and HSD17B1 protein levels in the serum PCOS and control (n = 40/each group) using RT-qPCR and ELISA. Estrone (E1), and androstenedione (A4), were significantly increased and estradiol (E2) was significantly decreased in PCOS. The relative expression shows, overexpression of miR-4430, miR-200b-5p and reduced expression of HSD17B1 gene as well as lower HSD17B1 protein level in PCOS. The in-silico functional annotation indicated that these miRNAs are involved pathways related to PCOS pathogenesis such as steroid synthesis and cell proliferation. Additionally, the diagnostic effectiveness by ROC analysis shows AUC for HSD17B1, miR-4430 and miR-200b-5p is 0.874, 0.869, and 0.943 respectively, reflecting a good diagnostic biomarker for PCOS. In conclusion, study indicates that overexpressed miR-4430 and miR-200b-5p probably limits the synthesis of estrone to estradiol via HSD17B1 in PCOS.