<p>CCNB1 Expedites the Progression of Cervical Squamous Cell Carcinoma via the Regulation by FOXM1</p>

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.

Bioinformatics Screening of Potential Biomarkers from mRNA Expression Profiles to Discover Drug Targets and Agents for Cervical Cancer

“…On the other hand, we reviewed 52 published articles associated with CC infections that provided transcriptome-guided hub proteins (genomic biomarkers) for cross-validation of the proposed key genes and the candidate drug agents. There were 255 hub genes reported in those 52 articles, with 7 hub proteins (AURKA, PCNA, CCNB1, CDC45, MCM2, TOP2A, CDK1) appearing in at least 5 articles ( Table S2 ) [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 23 , 24 , 25 , 26 , 27 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]. Five (AURKA, CCNB1, MCM2, TOP2A, and CDK1) of the seven reported hub proteins were found to be similar to our suggested seven KGs.…”

“…BRCA1 enhanced the sensitivity of cervical squamous cell carcinoma (CSCC) patients to cisplatin-based CCRT by up-regulating STAT1 to activate the JAK/STAT pathway [ 50 ]. CCNB1 played vital roles in the progression of CC through different signaling pathways [ 17 , 18 , 26 , 46 , 51 ]. CDK1 contributed to the occurrence and development of CSCC [ 18 , 23 , 25 , 26 , 27 , 40 , 41 , 44 , 46 ].…”

Bioinformatics analysis of differentially expressed genes and pathways in the development of cervical cancer

“…In addition, there were 6 common KEGG pathways in the CIN-CC group ( p < 0.01), namely, the adipocytokine signaling pathway, small cell lung cancer ( ITGA6 [ 25 ], PIAS3 , and LAMC2 [ 26 ]), pathways in cancer, the Toll-like receptor signaling pathway, graft versus host disease, and the TGF-beta signaling pathway [ 27 ]. There were 9 common KEGG pathways in the N-CC group ( p < 0.01), namely, the cell cycle ( PCNA , CDC25B , MCM3 , MCM5 , CDC6 [ 28 ], GSK3B , MCM6 , CHEK2 , PKMYT1 , CDC20 [ 29 ], PTTG1 , SMAD3 , CCNB1 [ 30 ], RBL1 , CDC7 [ 23 ], WEE1 , CDK2 [ 31 ], CCNA2 , and TTK ), nucleotide excision repair, the Toll-like receptor signaling pathway, prion diseases, spliceosome, DNA replication, proteasome, colorectal cancer, and pancreatic cancer. Moreover, GSEA showed that DNA mismatch repair (N-CIN), small cell lung cancer (CIN-CC), and the cell cycle (N-CC) were the most significantly enriched pathways ( P < 0.01, FDR < 0.05), and snapshots of the enrichment analysis are shown in Figs.…”

CCNB1 promotes the development of hepatocellular carcinoma by mediating DNA replication in the cell cycle

“…Various studies have showed that the overexpression of CCNB1 is common in many cancers, such as adrenocortical carcinoma, cervical carcinoma, stomach cancer, non-small cell lung cancer, and rhabdomyosarcoma. 12–16 A study showed that CCNB1 could promote the proliferation of pituitary adenomas and stimulate epithelial-to-mesenchymal transition. 17 In pancreatic cancer, CCNB1 silencing promotes cell senescence and suppresses cell proliferation by activating the p53 signaling pathway.…”