上调 miR-133a-3p 通过抑制 PI3K/AKT 信号通路促进肥胖 PCOS 患者颗粒细胞的卵巢胰岛素抵抗。

Up-regulation of miR-133a-3p promotes ovary insulin resistance on granulosa cells of obese PCOS patients via inhibiting PI3K/AKT signaling.

机构信息

Shandong University of Traditional Chinese Medicine, Jinan, China.

Integrative Medicine Center for Reproductive and Heredity, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, No. 42 Wenhuaxi Road, Jinan, China.

出版信息

BMC Womens Health. 2022 Oct 8;22(1):412. doi: 10.1186/s12905-022-01994-6.

DOI:10.1186/s12905-022-01994-6

PMID:36209087

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9548189/

Abstract

BACKGROUND

MicroRNAs are a type of non-coding single-stranded RNA, which is involved in the regulation of ovary insulin resistance (IR). This study aims to explore the underlying mechanisms of miR-133a-3p regulating ovary IR in obese polycystic ovary syndrome (PCOS).

METHODS

Granulosa cells (GCs) were extracted from follicular fluids of PCOS patients (obese PCOS group and non-obese PCOS group) and healthy women (control group). The expression of miR-133a-3p in GCs was detected by qRT-PCR. The targets and pathways of miR-133a-3p were predicted by bioinformatics analyses. The protein levels of PI3K, p-AKT, GLUT4, p-GSK-3β, and p-FOXO1 were measured by Western blotting.

RESULTS

MiR-133a-3p was highly expressed in GCs from PCOS patients, especially in obese PCOS patients. The protein levels of PI3K and p-AKT was downregulated in GCs from PCOS patients. There were 11 target genes of miR-133a-3p enriching in PI3K/AKT signaling pathway. miR-133a-3p mimic downregulated the expression of PI3K, p-AKT, and GLUT4, and upregulated the protein levels of p-GSK-3β and p-FOXO1. miR-133a-3p inhibitor presented the opposite effect of miR-133a-3p mimic.

CONCLUSION

MiR-133a-3p promotes ovary IR on GCs of obese PCOS patients via inhibiting PI3K/AKT signaling pathway. This study lays a foundation for further research on the mechanism of ovary IR in obese PCOS patients.

摘要

背景

MicroRNAs 是一种非编码的单链 RNA，参与调节卵巢胰岛素抵抗（IR）。本研究旨在探讨 miR-133a-3p 调节肥胖多囊卵巢综合征（PCOS）患者卵巢 IR 的潜在机制。

方法

从 PCOS 患者（肥胖 PCOS 组和非肥胖 PCOS 组）和健康女性（对照组）的卵泡液中提取颗粒细胞（GCs）。通过 qRT-PCR 检测 GCs 中 miR-133a-3p 的表达。通过生物信息学分析预测 miR-133a-3p 的靶标和途径。通过 Western blot 测定 PI3K、p-AKT、GLUT4、p-GSK-3β 和 p-FOXO1 的蛋白水平。

结果

miR-133a-3p 在 PCOS 患者的 GCs 中高表达，尤其是在肥胖 PCOS 患者中。PCOS 患者的 GCs 中 PI3K 和 p-AKT 的蛋白水平下调。miR-133a-3p 的 11 个靶基因富集在 PI3K/AKT 信号通路中。miR-133a-3p 模拟物下调 PI3K、p-AKT 和 GLUT4 的表达，并上调 p-GSK-3β 和 p-FOXO1 的蛋白水平。miR-133a-3p 抑制剂呈现出与 miR-133a-3p 模拟物相反的作用。