miR-3188 Regulates proliferation and apoptosis of granulosa cells by targeting KCNA5 in the polycystic ovary syndrome

Shan  Zhou; Liang Xia; Yuanyuan  Chen; Weiying  Guo; Jinxing  Hu

doi:10.18388/abp.2020_5441

Shan Zhou Department of Endocrinology, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo City, Zhejiang Province, 315010, China
Liang Xia Department of Gynecology, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo City, Zhejiang Province, 315010, China
Yuanyuan Chen Department of Endocrinology, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo City, Zhejiang Province, 315010, China
Weiying Guo Department of Endocrinology, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo City, Zhejiang Province, 315010, China
Jinxing Hu Department of Endocrinology, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo City, Zhejiang Province, 315010, China

DOI: https://doi.org/10.18388/abp.2020_5441

Abstract

Abnormal proliferation of granulosa cells is implicated in ovarian dysfunction and dysregulated folliculogenesis in the polycystic ovary syndrome (PCOS). Aberrant microRNA (miRNA) expression might contribute to disordered folliculogenesis and granulosa cell proliferation in PCOS. This study aimed to investigate the roles of miR-3188 in ovarian dysfunction, as well as the mechanism involved in granulosa cell proliferation in PCOS. Firstly, peripheral blood samples were isolated from PCOS patients and healthy controls, and qRT-PCR analysis demonstrated a dramatic increase in miR-3188 in PCOS patients when compared to the healthy controls. Secondly, miR-3188 overexpression increased cell viability of the granulosa-like tumor cell line (KGN). However, cell viability of KGN was repressed by interference with miR-3188. MiR-3188 promoted cell cycle of KGN through increasing cyclinD1 and decreasing p21 levels. Moreover, cell apoptosis was suppressed by miR-3188 in KGN, indicated by enhanced Bcl-2, and reduced Bax and cleaved caspase-3 levels, whereas knockdown of miR-3188 resulted in opposite effects. Lastly, potassium voltage-gated channel subfamily A member 5 (KCNA5) was verified as a target of miR-3188. KCNA5 expression was decreased and displayed negative correlation with miR-3188 levels in PCOS patients. Overexpression of KCNA5 attenuated the promotive effects of miR-3188 on cell viability and cell cycle in KGN. In conclusion, miR-3188, a key miRNA enhanced in PCOS, promoted granulosa cell proliferation through down-regulation of KCNA5, providing a new therapeutic target for PCOS.