环状RNA_0043314通过微小RNA-146b-3p/阿片生长因子13轴调控多囊卵巢综合征中卵巢颗粒细胞的增殖和凋亡

Circ_0043314 Modulates Proliferation and Apoptosis of Ovarian Granulosa Cells in Polycystic Ovarian Syndrome via the MicroRNA-146b-3p/Apelin 13 Axis.

作者信息

Wang Wei, Tan Luni, Ge Liang, Gou Ruiqiang, Gou Li, Liu Lin, Zhang Lili, Ma Xiaoling

机构信息

Key Laboratory for Reproductive Medicine and Embryo, The Reproductive Medicine Center, The First Hospital of Lanzhou University, Lanzhou, China.

The First Clinical Medical College of Lanzhou University, Lanzhou, China.

出版信息

Gynecol Obstet Invest. 2025;90(1):18-29. doi: 10.1159/000540097. Epub 2024 Jul 16.

DOI:10.1159/000540097

PMID:39008951

Abstract

INTRODUCTION

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women. At present, the pathogenesis has not been clarified, and the clinical application of drugs and lifestyle intervention may not prevent disease progression. This study aimed to investigate how circ_0043314 regulates ovarian granulosa cell biological functions to provide a theoretical basis for the treatment of patients with PCOS. MicroRNA (miR)-146b-3p/Apelin 13 axis was used to investigate the mechanism by which circ_0043314 regulated ovarian granulosa cell proliferation and apoptosis in PCOS via miR-146b-3p/Apelin 13 axis. Participants/Materials, Methods: Ovarian tissues (cortical tissues) from 35 PCOS patients and 35 normal controls, as well as HEK293T and human ovarian granulosa cell line (KGN, COV434), were included in this study. We examined the expression levels of circ_0043314, miR-146b-3p, and Apelin 13 in PCOS tissues. Ovarian granulosa cells were transfected with corresponding plasmids to clarify the influence of circ_0043314, miR-146b-3p, or Apelin 13 on proliferation and apoptosis of ovarian granulosa cells through MTT and flow cytometry assays. Moreover, the relationships among circ_0043314, miR-146b-3p, and Apelin 13 were analyzed through dual-luciferase and RNA immunoprecipitation assays.

RESULTS

Circ_0043314 and Apelin 13 were highly expressed and miR-146b-3p was lowly expressed in ovarian tissues of PCOS compared with non-PCOS controls. Downregulation of circ_0043314 or upregulation of miR-146b-3p hindered ovarian granulosa cell proliferation and advanced its apoptosis. Downregulation of miR-146b-3p reversed the impacts of downregulation of circ_0043314, and overexpression of Apelin 13 counteracted the influences of upregulation of miR-146b-3p in ovarian granulosa cells. Mechanically, circ_0043314 could bind to miR-146b-3p, and miR-146b-3p directly targeted and modulated Apelin 13 expression.

LIMITATIONS

This study was limited by the lack of animal experiments.

CONCLUSION

Our data demonstrated that circ_0043314 enhances ovarian granulosa cell proliferation and suppresses its apoptosis via miR-146b-3p/Apelin 13 axis.

摘要

引言

多囊卵巢综合征（PCOS）是女性常见的内分泌和代谢紊乱疾病。目前，其发病机制尚未阐明，药物临床应用和生活方式干预可能无法阻止疾病进展。本研究旨在探讨circ_0043314如何调节卵巢颗粒细胞生物学功能，为PCOS患者的治疗提供理论依据。采用微小RNA（miR）-146b-3p/阿片肽13轴，研究circ_0043314通过miR-146b-3p/阿片肽13轴调节PCOS中卵巢颗粒细胞增殖和凋亡的机制。

参与者/材料、方法：本研究纳入了35例PCOS患者和35例正常对照者的卵巢组织（皮质组织），以及人胚肾293T细胞和人卵巢颗粒细胞系（KGN、COV434）。我们检测了PCOS组织中circ_0043314、miR-146b-3p和阿片肽13的表达水平。用相应质粒转染卵巢颗粒细胞，通过MTT和流式细胞术检测circ_0043314、miR-146b-3p或阿片肽13对卵巢颗粒细胞增殖和凋亡的影响。此外，通过双荧光素酶和RNA免疫沉淀实验分析circ_0043314、miR-146b-3p和阿片肽13之间的关系。

结果

与非PCOS对照相比，PCOS患者卵巢组织中circ_0043314和阿片肽13高表达，miR-146b-3p低表达。下调circ_0043314或上调miR-146b-3p可抑制卵巢颗粒细胞增殖并促进其凋亡。下调miR-146b-3p可逆转下调circ_0043314的影响，过表达阿片肽13可抵消上调miR-146b-3p对卵巢颗粒细胞的影响。机制上，circ_0043314可与miR-146b-3p结合，miR-146b-3p直接靶向并调节阿片肽13的表达。