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Circ_0070987通过miR-139-5/CDH1轴促进多囊卵巢综合征中卵巢颗粒细胞的焦亡

Circ_0070987 Promotes Pyroptosis of Ovarian Granulosa Cells in Polycystic Ovarian Syndrome Through the miR-139-5/CDH1 Axis.

作者信息

Huang Rui, Gao Miao

机构信息

Department of Gynecology, Children's Hospital of Shanxi Province (Shanxi Province Maternal and Child Health Hospital), Taiyuan, 030006, China.

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Baotou Medical College, No. 30 Hudemulin Street, Qingshan District, Baotou, 014030, Inner Mongolia, China.

出版信息

Reprod Sci. 2025 Sep 5. doi: 10.1007/s43032-025-01966-9.

Abstract

PCOS refers to an endocrine and metabolic disorder that affects female individuals of reproductive age. Our study explores the potential mechanism of circ_0070987 on PCOS in regulating pyroptosis of ovarian GCs, providing new evidence for PCOS treatment. PCOS cell model was established. The expression of circ_0070987, line ELF2, miR-139-5p and CDH1 was detected. Cell viability was measured. The expression of IL-1β, IL-18, NLRP3, cleaved Caspase-1, GSDMD-N, and CDH1 was analyzed. Circ_0070987 was downregulated to verify its effect on pyroptosis. The binding of miR-139-5p to circ_0070987 and CDH1 was verified by dual-luciferase report assay. The role of circ_0070987 in pyroptosis of ovarian GCs in PCOS through the miR-139-5p/CDH1 axis was validated. After DHT treatment, cell viability of SVOG was decreased, and the expression of IL-1β, IL-18, circ_0070987, NLRP3, cleaved Caspase-1 and GSDMD-N was increased. DHT-induced pyroptosis of ovarian GCs was inhibited upon circ_0070987 downregulation. Mechanistically, circ_0070987 negatively regulated miR-139-5p, which targeted and inhibited CDH1. Inhibitory effect of circ_0070987 downregulation on pyroptosis of ovarian GCs in PCOS was reduced after miR-139-5p downregulation or CDH1 overexpression. In conclusion, circ_0070987 inhibits miR-139-5p expression and upregulates CDH1 expression, thus promoting pyroptosis of ovarian GCs in PCOS.

摘要

多囊卵巢综合征(PCOS)是一种影响育龄女性的内分泌和代谢紊乱疾病。我们的研究探讨了circ_0070987对PCOS调控卵巢颗粒细胞焦亡的潜在机制,为PCOS治疗提供新证据。建立了PCOS细胞模型。检测了circ_0070987、ELF2、miR-139-5p和CDH1的表达。测量了细胞活力。分析了白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)、NLRP3、裂解的半胱天冬酶-1(Caspase-1)、Gasdermin D-N(GSDMD-N)和CDH1的表达。下调circ_0070987以验证其对焦亡的影响。通过双荧光素酶报告基因检测验证了miR-139-5p与circ_0070987和CDH1的结合。验证了circ_0070987通过miR-139-5p/CDH1轴在PCOS卵巢颗粒细胞焦亡中的作用。双氢睾酮(DHT)处理后,SVOG细胞活力降低,IL-1β、IL-18、circ_0070987、NLRP3、裂解的Caspase-1和GSDMD-N的表达增加。下调circ_0070987可抑制DHT诱导的卵巢颗粒细胞焦亡。机制上,circ_0070987负调控miR-139-5p,miR-139-5p靶向并抑制CDH1。下调miR-139-5p或过表达CDH1后,circ_0070987下调对PCOS卵巢颗粒细胞焦亡的抑制作用减弱。总之,circ_0070987抑制miR-139-5p表达并上调CDH1表达,从而促进PCOS卵巢颗粒细胞焦亡。

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