A transcription factor that promotes proliferation, migration, invasion, and epithelial–mesenchymal transition of ovarian cancer cells and its possible mechanisms

Abstract

Abstract Background Ovarian cancer is one of the most common gynecological malignancies with the high morbidity and mortality. This study was aimed to explore the role of non-structure maintenance of chromosomes condensin I complex subunit H (NCAPH) in the progression of ovarian cancer (OC) and the transcription regulatory effects of GATA binding protein 3 (GATA3) on this gene. Methods Firstly, NCAPH and GATA3 expression in OC tissues and several human OC cell lines was, respectively, evaluated by TNMplot database and Western blot analysis. Then, NCAPH was silenced to assess the proliferation, migration, and invasion of OC cells in turn using CCK-8, wound healing, and transwell assays. Western blotting was used to determine the expression of epithelial--mesenchymal transition (EMT)-related proteins and PI3K/PDK1/AKT signaling proteins. The potential binding sites of GATA3 on NCAPH promoter were predicated using JASPAR database, which were verified by luciferase reporter assay and chromosomal immunoprecipitation. Subsequently, GATA3 was overexpressed to examine the biological functions of OC cells with NCAPH silencing. Results NCAPH and GATA3 expression was significantly upregulated in OC tissues and cell lines. NCAPH loss-of-function notably inhibited the proliferation, migration, invasion, and EMT of OC cells. Moreover, the expression of p-PI3K, PDK1, and p-AKT was downregulated after NCAPH knockdown. Furthermore, GATA3 was confirmed to bind to NCAPH promoter. GATA3 overexpression alleviated the inhibitory effects of NCAPH silencing on the proliferation, migration, invasion, EMT, and expression of proteins in PI3K/PDK1/AKT pathway of OC cells. Conclusion To sum up, NCAPH expression transcriptional activation by GATA3 accelerates the progression of OC via upregulating PI3K/PDK1/AKT pathway.