FOXM1 promotes proliferation in human hepatocellular carcinoma cells by transcriptional activation of CCNB1

• Published in: Biochemical and biophysical research communications Vol. 500; no. 4; pp. 924 - 929
• Main Authors: Chai, Na, Xie, Hua-hong, Yin, Ji-peng, Sa, Ke-di, Guo, Yi, Wang, Meng, Liu, Jun, Zhang, Xiao-fang, Zhang, Xiang, Yin, Hong, Nie, Yong-zhan, Wu, Kai-chun, Yang, An-gang, Zhang, Rui
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.06.2018
• Subjects: 60 APPLIED LIFE SCIENCES; Binding Sites; Carcinoma, Hepatocellular - diagnosis; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - mortality; CELL CYCLE; Cell Line, Tumor; CELL PROLIFERATION; Cyclin B1 - antagonists & inhibitors; Cyclin B1 - genetics; Cyclin B1 - metabolism; Forkhead Box Protein M1 - genetics; Forkhead Box Protein M1 - metabolism; FOXM1; Gene Expression Regulation, Neoplastic; Hep G2 Cells; HEPATOMAS; Human hepatocellular carcinoma; Humans; LIVER; Liver Neoplasms - diagnosis; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - mortality; MESSENGER-RNA; Prognosis; Promoter Regions, Genetic; Protein Binding; RNA, Messenger - antagonists & inhibitors; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Signal Transduction; Survival Analysis; TRANSCRIPTION FACTORS; Transcriptional Activation; Transcriptional regulation; Cell proliferation; Transcriptional regulation; FOXM1; Human hepatocellular carcinoma; Cell cycle
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2018.04.201

The transcription factor Forkhead box protein M1 (FOXM1) plays critical roles in cancer development and progression, including human hepatocellular carcinoma (HCC). However, the regulatory role and underlying mechanisms of FOXM1 is still limited. Here, we found that the high level expression of FOXM1 and CCNB1 is closely associated with poor prognosis in HCC patients. And FOXM1 and CCNB1 were overexpressed concomitantly in liver tumor tissues. Knockdown of FOXM1 significantly inhibited the expression levels of CCNB1 in HCC cell lines at both the mRNA and protein levels. Mechanistic studies revealed that FOXM1 binds directly to the promoter region of CCNB1 and regulates the expression levels of the CCNB1 gene in the transcriptional level. Furthermore, the loss of functional and rescue experiments showed that CCNB1 is essential for FOXM1-driven proliferation in HCC cells. In the present study, our results partially explained the dysregulated expression of FOXM1 play an important role in proliferation of human hepatocellular carcinoma cells via transcriptional activation of CCNB1 expression. And it also highlights a FOXM1/CCNB1 axis could be a potential target for the treatment of HCCs. •FOXM1 and CCNB1 are prognostic indicators in human hepatocellular carcinoma.•FOXM1 transcriptionally upregulates CCNB1 expression levels in HCC cells.•CCNB1 is essential for proliferation in HCC cells.•FOXM1 modulates HCC cell proliferation by targeting CCNB1.