circPTPN12/miR-21–5 p/∆Np63α pathway contributes to human endometrial fibrosis

eLife

Haixiang Sun¹  Ruotian Li²  Yun Cao³  Haining Lv³  Huiyan Wang³  Simin Yao³  Qianwen Wu³  Minmin Song³  Zhenhua Zhou³  Yali Hu³  Peipei Jiang³  Dan Liu³  Chenyan Dai³  Guangfeng Zhao³  Hui Zhu³  Yan Zhou⁴  Jingmei Wang⁵  Jianwu Dai⁶ 

[1] Center for Reproductive Medicine, Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China;Department of Laboratory Medicine, Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing, China;Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China;Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, United States;Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China;Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China;

关键词: endometrial epithelial cells;    endometrial fibrosis;    epithelial mesenchymal transition;    circPTPN12;    mir-21-5p;    ∆Np63α;    Human;    Mouse;   

DOI  :  10.7554/eLife.65735

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Emerging evidence demonstrates the important role of circular RNAs (circRNAs) in regulating pathological processes in various diseases including organ fibrosis. Endometrium fibrosis is the leading cause of uterine infertility, but the role of circRNAs in its pathogenesis is largely unknown. Here, we provide the evidence that upregulation of circPTPN12 in endometrial epithelial cells (EECs) of fibrotic endometrium functions as endogenous sponge of miR-21–5 p to inhibit miR-21–5 p expression and activity, which in turn results in upregulation of ΔNp63α to induce the epithelial mesenchymal transition (EMT) of EECs (EEC–EMT). In a mouse model of endometrium fibrosis, circPTPN12 appears to be a cofactor of driving EEC–EMT and administration of miR-21–5 p could reverse this process and improve endometrial fibrosis. Our findings revealed that the dysfunction of circPTPN12/miR-21–5 p/∆Np63α pathway contributed to the pathogenesis of endometrial fibrosis.

【 授权许可】

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