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miR-613 通过靶向 IGF-1 抑制细胞周期进程从而抑制人卵巢颗粒细胞的增殖。

miR-613 inhibits the proliferation of human ovarian granulosa cells by arresting cell cycle progression via the targeting of IGF-1.

机构信息

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.

出版信息

Mol Med Rep. 2021 Mar;23(3). doi: 10.3892/mmr.2020.11817. Epub 2021 Jan 5.

Abstract

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder, and microRNA (miRNA) molecules have been implicated in the pathological process of PCOS. The aim of the present study was to elucidate the regulatory effects of miR-613 and insulin-like growth factor-1 (IGF-1) on the pathological process of polycystic ovary syndrome (PCOS). The targeting of IGF-1 by miR-613 was investigated by dual-luciferase reporter assay. The regulatory effect of miR-613 on the mRNA and protein levels of IGF1 was determined by reverse transcription-quantitative PCR and western blot analysis. The regulatory effects of miR-613 and IGF-1 on the proliferation and cell cycle progression of KGN cells were evaluated by colony formation assay and flow cytometric analysis. The results revealed that miR-613 targeted IGF-1 and reduced its translational level. In KGN cells, miR-613 arrested cell cycle progression in the G2/M phase and downregulated the expression of cyclin D1 and CDK1. The overexpression of IGF-1 attenuated the inhibitory effects of miR-613 on cell cycle arrest, cyclin D1 and CDK1 expression, and the proliferation of KGN cells. In conclusion, the present study demonstrated that miR-613 targets IGF-1 and thus suppresses its translation. It arrests cell cycle progression and attenuates the proliferation of KGN cells via the targeting of IGF-1. Therefore, it is suggested that miR-613 and IGF-1 could potentially be diagnostic biomarkers and therapeutic targets for PCOS.

摘要

多囊卵巢综合征(PCOS)是一种常见的内分泌疾病,微小 RNA(miRNA)分子已被牵涉到 PCOS 的病理过程中。本研究旨在阐明 miR-613 和胰岛素样生长因子-1(IGF-1)对多囊卵巢综合征(PCOS)病理过程的调节作用。通过双荧光素酶报告基因实验研究 miR-613 对 IGF-1 的靶向作用。通过逆转录-定量 PCR 和 Western blot 分析确定 miR-613 对 IGF1 mRNA 和蛋白水平的调节作用。通过集落形成实验和流式细胞术分析评估 miR-613 和 IGF-1 对 KGN 细胞增殖和细胞周期进程的调节作用。结果表明,miR-613 靶向 IGF-1 并降低其翻译水平。在 KGN 细胞中,miR-613 使细胞周期停滞在 G2/M 期,并下调 cyclin D1 和 CDK1 的表达。IGF-1 的过表达减弱了 miR-613 对细胞周期阻滞、cyclin D1 和 CDK1 表达以及 KGN 细胞增殖的抑制作用。综上所述,本研究表明 miR-613 靶向 IGF-1 从而抑制其翻译。它通过靶向 IGF-1 使细胞周期停滞并减弱 KGN 细胞的增殖。因此,提示 miR-613 和 IGF-1 可能是 PCOS 的诊断生物标志物和治疗靶点。

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