MicroRNAs (miRNAs) regulate the functions of granulosa cells by interacting with their target mRNAs. Insulin receptor substrate 2 (IRS2) is one of the targets of miR-431 and can be regulated by ovarian hormones. However, the role of miR-431 and the associated signal transduction pathway in ovarian development has not been studied previously. In this study, we first analyzed the expression of miR-431 and IRS2 following stimulation with pregnant mare serum gonadotropin (PMSG) during the estrous cycle or different stages of ovarian development in mice. Subsequently, we investigated the role, function, and signaling pathway of miR-431 in the human granulosa cell line, COV434. The results showed that follicle stimulating hormone (FSH) gradually decreased miR-431 levels, induced IRS2, and promoted pAKT expression. Moreover, miR-431 overexpression and IRS2 knockdown attenuated AKT activation, inhibited cell proliferation, and decreased estradiol (E2) and progesterone (P4) synthesis. Further, luciferase reporter assay demonstrated that IRS2 was a direct target of miR-431. In conclusion, this study demonstrated that miR-431 regulates granulosa cell function through the IRS2/PI3K/AKT signaling pathway.

中文翻译：

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miR-431通过IRS2/PI3K/AKT信号通路调节颗粒细胞功能

MicroRNAs (miRNAs) 通过与其靶标 mRNA 相互作用来调节颗粒细胞的功能。胰岛素受体底物 2 (IRS2) 是 miR-431 的靶标之一，可受卵巢激素调节。然而，miR-431 和相关信号转导通路在卵巢发育中的作用以前尚未研究过。在这项研究中，我们首先分析了在小鼠发情周期或卵巢发育的不同阶段用孕马血清促性腺激素（PMSG）刺激后 miR-431 和 IRS2 的表达。随后，我们研究了 miR-431 在人颗粒细胞系 COV434 中的作用、功能和信号通路。结果表明，促卵泡激素（FSH）逐渐降低miR-431水平，诱导IRS2，促进pAKT表达。而且，miR-431 过表达和 IRS2 敲低减弱了 AKT 的激活，抑制了细胞增殖，并减少了雌二醇 (E2) 和孕酮 (P4) 的合成。此外，荧光素酶报告基因检测表明 IRS2 是 miR-431 的直接靶标。总之，本研究表明 miR-431 通过 IRS2/PI3K/AKT 信号通路调节颗粒细胞功能。