Huang Yi, Wang Yidan, Li Ruiyun, Liu Yongmei, Yang Yuan
The First Clinical Medical College of Lanzhou University, Lanzhou 730000, China.
Reproductive Medicine Center, The First Hospital of Lanzhou University, Lanzhou 730000, China.
iScience. 2024 Nov 28;27(12):111487. doi: 10.1016/j.isci.2024.111487. eCollection 2024 Dec 20.
Despite decades of research, the pathogenesis of endometriosis remains unclear. Recent studies have shown that microRNAs play an important role in this condition. In this study, we found that the expression level of miR-450b-5p was increased in ectopic endometrial tissues and that GA-binding protein A (GABPA) and HOXD10 expression levels were decreased. Overexpression of miR-450b-5p or knockdown of GABPA significantly promoted the proliferation and invasion of hEM15A cells and inhibited apoptosis and . Furthermore, GABPA was shown to be a direct target of miR-450b-5p and to bind directly to the promoter of the HOXD10 gene, regulating its transcription. Finally, intraperitoneal injection of HOXD10-overexpressing lentivirus in mice significantly attenuated ectopic endometrial lesions. miR-450b-5p directly targets GABPA, regulates expression of HOXD10, and promotes the growth of ectopic endometriotic lesions. Therefore, the miR-450b-5p/GABPA/HOXD10 signaling pathway may be a potential target for treatment of heterotopic endothelial cell disease.
尽管经过数十年的研究，子宫内膜异位症的发病机制仍不清楚。最近的研究表明，微小RNA在这种疾病中起重要作用。在本研究中，我们发现异位子宫内膜组织中miR-450b-5p的表达水平升高，而GA结合蛋白A（GABPA）和HOXD10的表达水平降低。miR-450b-5p的过表达或GABPA的敲低显著促进了hEM15A细胞的增殖和侵袭，并抑制了细胞凋亡。此外，GABPA被证明是miR-450b-5p的直接靶点，并直接与HOXD10基因的启动子结合，调节其转录。最后，在小鼠腹腔内注射过表达HOXD10的慢病毒显著减轻了异位子宫内膜病变。miR-450b-5p直接靶向GABPA，调节HOXD10的表达，并促进异位子宫内膜异位病变的生长。因此，miR-450b-5p/GABPA/HOXD10信号通路可能是治疗异位内皮细胞疾病的潜在靶点。
