Deregulation of RUNX2 by miR-320a deficiency impairs steroidogenesis in cumulus granulosa cells from polycystic ovary syndrome (PCOS) patients.

Deregulation of epigenetic modification by microRNAs (miRNAs) contributes to the development of estrogen deficiency, a hallmark of the multigenic endocrine disorder polycystic ovary syndrome (PCOS), but its etiology remains unclear. Previous study has pointed to a tight association between miR-320a expression and oocyte development in human follicular fluid. Given that the bi-directional communication existing between cumulus cells (CCs) and follicular fluid is essential for ovarian steroidogenesis and CCs are the main site where estrogen is finally synthesized, it is intriguing to know whether miR-320a have any regulatory roles in this unique cell. Here we report that miR-320a expression is significantly down-regulated in primary CCs from PCOS patients and this down-regulation promotes estrogen deficiency in CCs. From a mechanistic standpoint, IGF1 regulates miR-320a expression in CCs, and miR-320a could potentiate the steroidogenesis in CCs through modulation of CYP11A1 and CYP19A1 expression, by directly targeting 3'untranslated region (3'UTR) of the osteogenic transcription factor RUNX2. Overall, our results strongly suggest that deregulation of miR-320a/RUNX2/CYP11A1 (CYP19A1) cascade plays an important role in the development of estrogen deficiency in human CCs. Testing patients for miR-320a/RUNX2 expression ratios may provide more accurate diagnostic information and could influence the recommended course of treatment for PCOS.