miR-145通过调控人子宫内膜基质细胞OCT4的表达促进子宫内膜异位症的发展机制

目的 通过体外细胞试验探讨miR-145在子宫内膜异位症（Endometriosis,EMs）中的调控机制。方法 蛋白印迹检测OCT4等相关蛋白的表达水平,通过相关分析和双荧光素酶报告试验用于评估miR-145和OCT4之间的关联,CCK8试剂盒检测细胞活力,流式细胞术检测细胞凋亡,通过Transwell法检测hESCs的迁移。结果 前期临床试验发现异位子宫内膜组织miR-145表达上调,OCT4表达下调。在细胞实验中,miR-145过表达可显著促进hESCs的增殖和迁移（P <0.01）,但抑制hESCs的凋亡（P <0.05）。miR-145模拟物转染hESCs后,OCT4、Bax和MMP1等蛋白表达水平降低（P <0.01）,Bcl-2蛋白表达水平升高（P <0.05）。敲除miR-145逆转了上述结果,并通过靶向OCT4显著抑制了hESCs的增殖（P <0.05）。结论 研究结果表明,miR-145表达增加通过抑制OCT4蛋白表达,可能通过促进子宫内膜基质细胞上皮细胞间质转化（Epithelial-mesenchymal Transition,EM...

miR-145 Regulates the Expression of OCT4 in Human Endometrial Stromal Cells and Promotes the Development of Endometriosis

  Objective  To further explore the regulatory mechanism of miR-145 in Endometriosis （EMs） through cell experiments.  Methods  miR-145 or octamer-binding transcription factor 4 （OCT4）gene and protein expression levels in cells were examined using reverse transcription-quantitative PCR and western blotting, respectively. Correlation analyses and dualluciferase reporter assays were performed to assess the association between miR-145 and OCT4. A Cell Counting Kit-8 assay was performed to test cell viability, while cell apoptosis was measured using ?ow cytometry. Moreover, the migration of hESCs was measured via Transwell assays.   Results  In cell assays, overexpression of miR-145 signifcantly promoted proliferation and migration （P < 0.01）, but inhibited the apoptosis of hESCs （P < 0.05）. Furthermore, the transfection of hESCs with miR-145 mimics decreased the protein expression levels of OCT4, Bax and MMP1 （P < 0.01）, as well as increased the protein expression of Bcl-2. However, knockdown of miR-145 reversed these results and significantly inhibited the proliferation of hESCs by targeting OCT4 （P < 0.05）.   Conclusion  The present results suggested that knockdown of miR-145 signifcantly suppressed the development of EMs by targeting OCT4, which may serve as a potential target for the treatment of EMs.