KIF4A knockdown suppresses ovarian cancer cell proliferation and induces apoptosis by downregulating BUB1 expression.

Abstract

Ovarian cancer is one of the most common lethal gynecological malignancies worldwide. Abnormal kinesin family member 4A (KIF4A) expression has been implicated in ovarian cancer progression; however, the potential mechanism underlying KIF4A in ovarian cancer is not completely understood. The present study aimed to clarify the molecular basis of KIF4A in ovarian cancer. KIF4A and budding uninhibited by benzimidazoles 1 (BUB1) expression levels were detected via reverse transcription-quantitative PCR and western blotting. Cell Counting Kit-8, colony formation, wound healing, TUNEL and flow cytometry assays were performed to assess cell proliferation, migration, apoptosis and cell cycle distribution, respectively. Ki67 expression levels were detected by conducting immunofluorescence assays. The expression levels of migration- and apoptosis-related proteins were measured via western blotting. A co-immunoprecipitation assay was conducted to determine the association between KIF4A and BUB1. The results demonstrated that KIF4A was expressed at significantly higher levels in ovarian cancer cell lines compared with IOSE-80 cells. Compared with the short hairpin RNA-negative control group, KIF4A knockdown significantly inhibited cell viability, colony formation and migration, and markedly induced cell apoptosis. The results indicated that KIF4A could bind to BUB1 and regulate BUB1 expression. BUB1 overexpression weakened KIF4A knockdown-mediated effects on cell viability, colony formation, migration and apoptosis. Overall, the present study demonstrated that KIF4A knockdown suppressed ovarian cancer progression by regulating BUB1, and suggested the potential value of KIF4A and BUB1 as therapeutic targets for ovarian cancer.