LncRNA CDKN2B-AS1 promotes epithelial-mesenchymal transition by targeting the miR-424-5p/AKT3 axis in ovarian endometriosis

ABSTRACT Research question Endometriosis is a common and complicated gynecologic disease. Long no-coding RNA CDKN2B-AS1 plays a crucial role in the development and progression of several cancers. However, whether CDKN2B-AS1 contributes to endometriosis remains unknown. Design Cellular proliferation, invasion and DNA synthesis abilities were assessed by CCK8, transwell and EdU assays. The expression of EMT markers and three isoforms of AKT were detected using western blot. Real-time PCR was used to determine the relative expression levels of CDKN2B-AS1 and candidate miRNAs in ectopic, eutopic endometria and normal endometrial tissues. The relationship between CDKN2B-AS1 and miRNA were determined by luciferase reporter assays. Results In the present study, we found that the relative expression level of CDKN2B-AS1 was up-regulated in eutopic and ectopic endometria. In endometrial stromal cells and Ishikawa cells, CDKN2B-AS1 overexpression promoted cellular proliferation and invasion, and increased the protein expression of vimentin but decreased the expression of E-cadherin. miR-424-5p was confirmed the target of CDKN2B-AS1 through bioinformatics tools and luciferase reporter assays. In addition, the enhanced effect of cellular phenotype of CDKN2B-AS1 overexpression was significantly attenuated by miR-424-5p overexpression. Furthermore, we proved that miR-424-5p could directly target AKT3 through luciferase reporter assay. Mechanistically, CDKN2B-AS1 promoted EMT by regulating the miR-424-5p/AKT3 axis. Conclusions Our findings confirmed the cellular mechanism of CDKN2B-AS1 in endometriosis and provided CDKN2B-AS1 may be a potential target for ovarian endometriosis therapy.