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Overexpressed miR-135b in the ovaries of PCOS promotes granulosa cell proliferation by inhibiting Hippo signaling pathway

文献类型：期刊论文

作者Ren, Shimin2,4; Chen, Liyang3; Xiao, Ni1; Huang, Xueying1; Wang, Xian2,4; Li, Yang2,4; Zhang, Bing1,5; Wang, Wenjuan6; Huang, Xin6
刊名JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
出版日期2025-10-04
页码15
关键词Apoptosis Hippo pathway LATS2 MiR-135b PCOS Proliferation
ISSN号1058-0468
DOI10.1007/s10815-025-03687-z
英文摘要BackgroundPolycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder, characterized by ovarian structural abnormalities that lead to ovulatory dysfunction. The Hippo signaling pathway is crucial in regulating ovarian enlargement and cortical thickening, which are hallmarks of PCOS, although the regulatory mechanisms remain unclear.MethodsWe assessed the expression of miR-135b and its target gene LATS2 (large tumor suppressor 2) in granulosa cells from both PCOS and normal ovaries using quantitative PCR. Dual-luciferase assays confirmed their direct interaction. The expression and localization of YAP (yes-associated protein), a key effector of the Hippo pathway, were examined through immunofluorescence in granulosa cells (GCs) from both groups. Additionally, the impact of miR-135b overexpression or inhibition on Hippo pathway genes was investigated in the KGN granulosa cell line, with changes in cell proliferation and apoptosis analyzed by cell proliferation assay and flow cytometry.ResultsMiR-135b was significantly upregulated (9.15-fold) in PCOS granulosa cells and targeted LATS2, a critical Hippo pathway regulator. Dual-luciferase assays confirmed the miR-135b binding site in the 3 '-UTR of LATS2. Mechanistically, high miR-135b expression reduced LATS2 levels, impairing YAP phosphorylation, promoting nuclear translocation of unphosphorylated YAP, and driving excessive granulosa cell proliferation.ConclusionOur findings suggest that miR-135b overexpression in PCOS ovaries contributes to abnormal granulosa cell proliferation by inhibiting the Hippo pathway. This study enhances our understanding of ovarian abnormalities in PCOS and identifies miR-135b as a potential biomarker and therapeutic target for the disorder.
WOS关键词INTESTINAL REGENERATION ; IDENTIFICATION ; CONSENSUS ; CRITERIA ; GENE
资助项目Shanghai Natural Science Foundation[23ZR1450200] ; National Natural Science Foundation of China[31671049] ; National Natural Science Foundation of China[32371005] ; Shanghai Municipal Science and Technology Major Project[184319071000] ; Shanghai Municipal Science and Technology Major Project[19140903102] ; National Natural Science Foundation[82271582] ; Biomedical Engineering Special Program of 'Science and Technology Innovation Projects' fromtion of the Hippo signaling pathway
WOS研究方向Genetics & Heredity ; Obstetrics & Gynecology ; Reproductive Biology
语种英语
WOS记录号WOS:001586439400001
出版者SPRINGER/PLENUM PUBLISHERS
源URL[http://119.78.100.183/handle/2S10ELR8/321603]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者Li, Yang; Zhang, Bing; Wang, Wenjuan; Huang, Xin
作者单位1.Tongji Univ, Shanghai Matern & Infant Hosp 1, Shanghai Inst Maternal Fetal Med & Gynecol Oncol, Shanghai Key Lab Maternal Fetal Med,Sch Med, Shanghai 201204, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Southeast Univ, Sch Publ Hlth, Key Lab Environm Med Engn & Educ Minist, Nanjing 210009, Jiangsu, Peoples R China
4.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Jiangsu, Peoples R China
5.Fudan Univ, Hosp Obstet & Gynecol, Shanghai Med Coll, Shanghai, Peoples R China
6.Shanghai Jiao Tong Univ, Xinhua Hosp, Reprod Med Ctr, Sch Med, Shanghai 200082, Peoples R China
推荐引用方式
GB/T 7714		 Ren, Shimin,Chen, Liyang,Xiao, Ni,et al. Overexpressed miR-135b in the ovaries of PCOS promotes granulosa cell proliferation by inhibiting Hippo signaling pathway[J]. JOURNAL OF ASSISTED REPRODUCTION AND GENETICS,2025:15.
APA Ren, Shimin.,Chen, Liyang.,Xiao, Ni.,Huang, Xueying.,Wang, Xian.,...&Huang, Xin.(2025).Overexpressed miR-135b in the ovaries of PCOS promotes granulosa cell proliferation by inhibiting Hippo signaling pathway.JOURNAL OF ASSISTED REPRODUCTION AND GENETICS,15.
MLA Ren, Shimin,et al."Overexpressed miR-135b in the ovaries of PCOS promotes granulosa cell proliferation by inhibiting Hippo signaling pathway".JOURNAL OF ASSISTED REPRODUCTION AND GENETICS (2025):15.

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来源：上海药物研究所

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