TOPK inhibits TNF-α-induced granulosa cell apoptosis via regulation of SIRT1/p53

T-LAK cell originated protein kinase (TOPK) has been shown to regulate proliferation, invasion or migration of various cancer cells. However, the role of TOPK in follicle environments remains unknown. Here we reveal that TOPK inhibits TNF-α-induced human granulosa COV434 cell apoptosis. The expression of TOPK were increased in COV434 cells in response to TNF-α. TOPK inhibition also decreased TNF-α-induced SIRT1 expression but promoted TNF-α-induced p53 acetylation and expression of PUMA or NOXA. Accordingly, TOPK inhibition attenuated TNF-α-mediated SIRT1 transcriptional activity. In addition, SIRT1 inhibition augmented acetylation of p53 or expression of PUMA and NOXA in response to TNF-α, leading to COV434 cell apoptosis. We conclude that TOPK suppresses TNF-α-induced COV434 granulosa cell apoptosis via regulation of p53/SIRT1 axis, suggesting a potential role of TOPK in regulation of ovarian follicular development. [Display omitted] •TNF-α induces apoptosis of human granulosa cell line, COV434.•TOPK inhibition downregulates SIRT1 expression in TNF-α response.•Suppression of SIRT1 activity enhances TNF-α-induced p53 activity to increase expression of PUMA or NOXA.•SIRT1 inhibition enhances granulosa cell apoptosis in response to TNF-α.