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.
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.
Acta Biochim Pol. 2021 Feb 3;68(1):83-89. doi: 10.18388/abp.2020_5441.
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.
颗粒细胞的异常增殖与多囊卵巢综合征（PCOS）中的卵巢功能障碍和滤泡发育失调有关。异常的 microRNA（miRNA）表达可能导致 PCOS 中滤泡发育障碍和颗粒细胞增殖。本研究旨在探讨 miR-3188 在卵巢功能障碍以及 PCOS 中颗粒细胞增殖中的作用机制。首先，从 PCOS 患者和健康对照者中分离外周血样本，qRT-PCR 分析表明，与健康对照者相比，PCOS 患者的 miR-3188 明显增加。其次，miR-3188 过表达增加了颗粒状肿瘤细胞系（KGN）的细胞活力。然而，miR-3188 的干扰抑制了 KGN 的细胞活力。miR-3188 通过增加细胞周期蛋白 D1（cyclinD1）和降低 p21 水平促进 KGN 的细胞周期。此外，miR-3188 在 KGN 中抑制细胞凋亡，表现为 Bcl-2 增加，Bax 和 cleaved caspase-3 减少，而 miR-3188 的敲低则产生相反的效果。最后，钾电压门控通道亚家族 A 成员 5（KCNA5）被验证为 miR-3188 的靶标。在 PCOS 患者中，KCNA5 的表达减少且与 miR-3188 水平呈负相关。KCNA5 的过表达减弱了 miR-3188 对 KGN 细胞活力和细胞周期的促进作用。总之，miR-3188 是 PCOS 中增强的关键 miRNA，通过下调 KCNA5 促进颗粒细胞增殖，为 PCOS 提供了一个新的治疗靶点。
