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Targeting circPTPN12/1 miR-21-5p/ΔNp63α pathway as a therapeutic strategy for human endometrial fibrosis

Song, M.; Zhao, G.; Sun, H.; Yao, S.; Zhou, Z.; Jiang, P.; Wu, Q.; Zhu, H.; Wang, H.; Dai, C.; Wang, J.; Li, R.; Cao, Y.; Lv, H.; Liu, D.; Dai, J.; Zhou, Y.; Hu, Y.

2021-04-16 molecular biology
10.1101/2021.04.15.440082 bioRxiv
Show abstract

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-21-5p to inhibit miR-21-5p expression and activity, which in turn results in upregulation of {Delta}Np63 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. Our findings reveal the novel mechanism in the pathogenesis of endometrium fibrosis and the potential therapeutic strategy for endometrium fibrosis via targeting circPTPN12/miR-21-5p/{Delta}Np63 pathway.

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