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miR-17-5p-Mediated RNA Activation Upregulates KPNA2 Expression and Inhibits High-Glucose-Induced Apoptosis of Sheep Granulosa Cells

文献类型： 外文期刊

作者： Wang, Yong 1 ; Tian, Feng 1 ; Yue, Sicong 2 ; Li, Jiuyue 1 ; Li, Ao 2 ; Liu, Yang 1 ; Liang, Jianyong 1 ; Gao, Yuan 1 ; Xue, Shuyuan 1 ;

作者机构： 1.Inner Mongolia Acad Agr & Anim Husb Sci, Hohhot 010030, Peoples R China

2.Hebei Agr Univ, Coll Anim Sci & Technol, Baoding 071000, Peoples R China

关键词： high glucose; granulosa cell; miR-17-5p; KPNA2; apoptosis

期刊名称：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES （ 影响因子：4.9； 五年影响因子：5.7 ）

ISSN： 1661-6596

年卷期： 2025 年 26 卷 3 期

页码：

收录情况： SCI

摘要： The glucose metabolism homeostasis in the follicular fluid microenvironment plays an important role in follicular maturation and ovulation, and excessively high or low glucose concentrations have adverse effects on the differentiation of follicular granulosa cells (GCs). However, a limited number of microRNAs (miRNA) have been reported to be involved in glucose-stimulated GCs differentiation. In this study, we characterized the miRNA expression profiles of sheep ovarian GCs cultured in high-glucose and optimal glucose concentrations and focused on a differentially expressed miRNA: miR-17-5p, which may be involved in regulating high-glucose-induced GC apoptosis by targeting KPNA2. We found that overexpression of miR-17-5p significantly promoted GCs proliferation and inhibited cell apoptosis, while downregulated the mRNA and protein expression of apoptosis-related makers (Bax, Caspase-3, Caspase-9, and Bcl-2). In contrast to the classical mechanism of miRNA silencing target gene expression, miR-17-5p overexpression significantly upregulated the expression of target gene KPNA2. A dual luciferase reporter gene assay verified the targeted binding relationship between miR-17-5p and KPNA2 promoter. Meanwhile, overexpression of KPNA2 further promoted the downregulation of apoptosis-related genes driven by miR-17-5p mimics. Knockdown of KPNA2 blocked the inhibitory effect of miR-17-5p mimics on the expression of apoptosis-related genes. Our results demonstrated that miR-17-5p activated the KPNA2 promoter region and upregulated KPNA2 expression, thereby inhibiting GCs apoptosis under high glucose.

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