CCNB1 Expedites the Progression of Cervical Squamous Cell Carcinoma via the Regulation by FOXM1.

ABSTRACT: Background: Cervical squamous cell carcinoma (CSCC) is responsible for 80-85% of cervical cancer. Cyclin B1 (CCNB1) represents a hub gene during the development of cervical cancer. However, the oncogenic role of CCNB1 in CSCC remains unclear. Our study aims to explore the mechanism underlying CCNB1 regulation on cell cycle progression in CSCC cells.

Methods: First, we analyzed differentially expressed genes from CSCC dataset GSE63678 and conducted gene function enrichment analysis. Subsequently, CCNB1 expression was knocked down in CSCC cell lines to assess cell proliferation, apoptosis, and cell cycle distribution. After the validation of the binding relationship between forkhead box protein M1 (FOXM1) and the promoter of CCNB1, the effect of FOXM1 on CCNB1 expression and on CSCC cell growth and apoptosis was verified. We further analyzed the histone ChIP-Seq data of CCNB1 in CSCC cells and measured the acetylation levels of the CCNB1 promoter histones.

Results: CCNB1 was overexpressed in CSCC tissues and cells, and CCNB1 silencing inhibited the growth of CSCC cells, and promoted cell cycle arrest and apoptosis. FOXM1 potentiated CCNB1 transcription by binding to its promoter and recruiting CBP/P300, a histone acetyltransferase. Further increasing FOXM1 expression or increasing P300 activity in CSCC cells with CCNB1 knockdown elevated CCNB1 expression and proliferation and cell cycle progression of CSCC cells. Knockdown of CCNB1 activated the p53 pathway in cells.

Conclusion: FOXM1 inhibited the activation of the p53 pathway by recruiting CBP/P300, which promoted the transcription of CCNB1, resulting in the growth and cell cycle progression of CSCC cells.

SUBMITTER: Li S 

PROVIDER: S-EPMC7721124 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature