Zhao Qian, Han Bing, Zhang Ying, Su Ke, Wang Chunfang, Hai Panpan, Bian Aiping, Guo Ruixia
Department of Gynecology, The First Affiliated Hospital of Zhengzhou University Zhengzhou, Henan Province, China.
Am J Transl Res. 2020 Oct 15;12(10):6136-6148. eCollection 2020.
This study aimed to find out the regulatory mechanism of miR-194-5p targeting STAT1/mTOR signaling pathway on the biological characteristics of endometrial epithelium cells from mice with endometriosis (EMs).
Mouse model of EMs was constructed to observe the histopathological changes of endometrium HE staining. The targeting relationship between miR-194-5p and STAT1 was verified by bioinformatics website as well as dual-luciferase reporter assay. The expressions of miR-194-5p and STAT1 in the cells were detected by qRT-PCR, then, the proliferative activity, invasion ability, apoptosis and cycle of cells were determined after overexpression of miR-194-5p, or down-regulation of miR-194-5p and STAT1.
In the ectopic endometrial epithelial cells, the expression of miR-194-5p was reduced, while the expression of STAT1 was significantly elevated. Overexpression of miR-194-5p or down-regulation of STAT1 significantly inhibited the proliferation and invasion and promoted apoptosis of ectopic endometrial cells. While down-regulation of miR-194-5p reversed the results, and inhibition of STAT1 partially reversed the effects partially.
The miR-194-5p inhibits mTOR signaling pathway by inhibiting the expression of STAT1 gene, so as to inhibit the proliferation and invasion, as well as to promote the apoptosis of ectopic endometrial epithelial cells in mice with EMs.
本研究旨在探究miR-194-5p靶向信号转导和转录激活因子1(STAT1)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路对子宫内膜异位症(EMs)小鼠子宫内膜上皮细胞生物学特性的调控机制。
构建EMs小鼠模型,通过苏木精-伊红(HE)染色观察子宫内膜的组织病理学变化。利用生物信息学网站及双荧光素酶报告基因检测法验证miR-194-5p与STAT1的靶向关系。采用实时定量聚合酶链反应(qRT-PCR)检测细胞中miR-194-5p和STAT1的表达,然后在过表达miR-194-5p、下调miR-194-5p和STAT1后,检测细胞的增殖活性、侵袭能力、凋亡及周期。
在异位子宫内膜上皮细胞中,miR-194-5p表达降低,而STAT1表达显著升高。过表达miR-194-5p或下调STAT1可显著抑制异位子宫内膜细胞的增殖和侵袭,并促进其凋亡。而下调miR-194-5p可逆转上述结果,抑制STAT1可部分逆转上述作用。
miR-194-5p通过抑制STAT1基因的表达来抑制mTOR信号通路,从而抑制异位子宫内膜上皮细胞的增殖和侵袭,并促进其凋亡。