Graduate School, Fujian Medical University, Fuzhou, China.
The 900th hospital of the Joint Service Support Force of the Chinese People's Liberation Army, Fuzhou, China.
J Ovarian Res. 2020 Aug 9;13(1):90. doi: 10.1186/s13048-020-00686-9.
MiRNAs play important roles in the development of ovarian cancer, activation of primitive follicles, follicular development, oocyte maturation and ovulation. In the present study, we investigated the specific role of miR-23a in cov434 cells.
Downregulation of miR-23a was observed in serum of PCOS patients compared with the healthy control, suggesting the inhibitory effect of miR-23a in PCOS. MiR-23a was positively correlated with Body Mass Index (BMI) and negatively correlated with Luteinizing hormone (LH), Testostrone (T), Glucose (Glu) and Insulin (INS) of PCOS patients. MiR-23a mimic inhibited the proliferation and promoted apoptosis of human cov434 cells. In addition, flow cytometry assay confirmed that miR-23a blocked cell cycle on G0/G1 phase. MiR-23a inhibitor showed opposite results. Furthermore, double luciferase reporter assay proved that miR-23a could bind to the 3'UTR of FGD4 directly through sites predicted on Target Scan. FGD4 level was significantly suppressed by miR-23a mimic, but was significantly enhanced by miR-23a inhibitor. We further proved that miR-23a increased the expression of activated CDC42 (GTP bround) and p-PAK-1, suggesting that miR-23a induced cell cycle arrest through CDC42/PAK1 pathway.
In conclusion, our study reveals that miR-23a participates in the regulation of proliferation and apoptosis of cov434 cells through target FGD4, and may play a role in the pathophysiology of PCOS.
miRNAs 在卵巢癌的发生发展、原始卵泡的激活、卵泡发育、卵母细胞成熟和排卵中发挥着重要作用。在本研究中，我们研究了 miR-23a 在 cov434 细胞中的特定作用。
与健康对照组相比，PCOS 患者的血清中观察到 miR-23a 的下调，表明 miR-23a 在 PCOS 中具有抑制作用。miR-23a 与 PCOS 患者的体重指数（BMI）呈正相关，与黄体生成素（LH）、睾丸酮（T）、葡萄糖（Glu）和胰岛素（INS）呈负相关。miR-23a 模拟物抑制了人 cov434 细胞的增殖并促进了细胞凋亡。此外，流式细胞术检测证实 miR-23a 将细胞周期阻滞在 G0/G1 期。miR-23a 抑制剂则表现出相反的结果。此外，双荧光素酶报告基因检测证实 miR-23a 可以通过 Target Scan 预测的位点直接与 FGD4 的 3'UTR 结合。miR-23a 模拟物显著抑制了 FGD4 水平，但 miR-23a 抑制剂则显著增强了 FGD4 水平。我们进一步证明 miR-23a 增加了激活的 CDC42（GTP 结合）和 p-PAK-1 的表达，表明 miR-23a 通过 CDC42/PAK1 通路诱导细胞周期停滞。
总之，我们的研究表明，miR-23a 通过靶标 FGD4 参与 cov434 细胞增殖和凋亡的调节，可能在 PCOS 的病理生理学中发挥作用。
