circPTPN12/miR-21-5 p/∆Np63α pathway contributes to human endometrial fibrosis.
circPTPN12/miR-21-5 p/∆Np63α pathway contributes to human endometrial fibrosis.
复制标题
作者：
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
新出现的证据表明环状RNA（circRNA）在调节包括器官纤维化在内的各种疾病的病理过程中的重要作用。子宫内膜纤维化是导致子宫不育的主要原因，但circRNA在其发病机制中的作用在很大程度上是未知的。在此，我们提供证据表明，在纤维化子宫内膜的子宫内膜上皮细胞（EECs）中，circPTPN 12的上调作为miR-21 - 5 p的内源性海绵发挥作用，抑制miR-21-5 p的表达和活性，从而导致Δ Np 63 α的上调，从而诱导EECs的上皮间质转化（EEC-EMT）。在子宫内膜纤维化的小鼠模型中，circPTPN 12似乎是驱动EEC-EMT的辅因子，并且施用miR-21-5 p可以逆转该过程并改善子宫内膜纤维化。结果提示，circPTPN 12/miR-21-5 p/miR-21-5 p63 α通路功能异常可能参与了子宫内膜纤维化的发病机制。
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.