The Second Department of Gynecologic Oncology, Hunan Cancer Hospital (The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University), Changsha 410013, PR China.
Department of Rehabilitation Medicine, Xiangya Hospital, Central South University, Changsha 410008, PR China.
Life Sci. 2021 Jan 15;265:118757. doi: 10.1016/j.lfs.2020.118757. Epub 2020 Nov 13.
Recent evidence has suggested the important implications of microRNAs (miRNAs) in the processes of proliferation and tissue remodeling in endometriosis (EMS). We therefore aim to determine the role of miR-202-3p in the pathophysiology of EMS and its underlying mechanisms.
Experimental endometriosis was induced in ovariectomized mice implanted with a slow-release 17-β estradiol capsule. Eutopic endometrial stromal cells (euESCs) were isolated and assayed for proliferative, invasive and apoptotic properties by EdU staining, Transwell assays, and flow cytometry. The invasive and apoptotic features in the endometrium of mice with EMS in vivo were evaluated by using immunohistochemical staining and TUNEL assays.
miR-202-3p was observed to be downregulated in the endometrial tissues of EMS patients. MiR-202-3p was also found to target YAP1 which resulted in reduced euESC proliferation and invasion and increased apoptosis. YAP1 was able to phosphorylated STAT3 which consequently upregulated S100A6 to promote the proliferative and invasive abilities of euESCs. MiR-202-3p was thereby proposed to act as an inhibitor of proliferation and tissue damage in the in vivo setting of EMS, its effects however, were able to be counteracted byS100A6, which reversed the effects of miR-202-3p on tissue injury and cell proliferation.
Our data together evidenced that miR-202-3p targeted YAP1 to reduce STAT3-mediated S100A6 whereby preventing the progression of EMS.
最近的证据表明微小 RNA（miRNA）在子宫内膜异位症（EMS）的增殖和组织重塑过程中具有重要意义。因此，我们旨在确定 miR-202-3p 在 EMS 病理生理学及其潜在机制中的作用。
通过给卵巢切除的小鼠植入缓释 17-β 雌二醇胶囊来诱导实验性 EMS。分离和分析在位子宫内膜基质细胞（euESCs）的增殖、侵袭和凋亡特性，通过 EdU 染色、Transwell 分析和流式细胞术进行检测。通过免疫组织化学染色和 TUNEL 分析评估体内 EMS 小鼠子宫内膜的侵袭和凋亡特征。
miR-202-3p 在 EMS 患者的子宫内膜组织中观察到下调。miR-202-3p 还靶向 YAP1，导致 euESC 增殖和侵袭减少，凋亡增加。YAP1 能够磷酸化 STAT3，从而上调 S100A6 以促进 euESCs 的增殖和侵袭能力。因此，miR-202-3p 被认为是在 EMS 的体内环境中抑制增殖和组织损伤的抑制剂，但其作用可被 S100A6 抵消，S100A6 逆转了 miR-202-3p 对组织损伤和细胞增殖的作用。
我们的数据共同表明，miR-202-3p 靶向 YAP1 以减少 STAT3 介导的 S100A6，从而阻止 EMS 的进展。
