Elevated expression of FoxM1 promotes the tumor cell proliferation in hepatocellular carcinoma

• Published in: Tumor biology Vol. 37; no. 1; pp. 1289 - 1297
• Main Authors: Yu, Min, Tang, Zheng, Meng, Fandi, Tai, Minghui, Zhang, Jingyao, Wang, Ruitao, Liu, Chang, Wu, Qifei
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.01.2016; Springer Nature B.V
• Subjects: Aged; Animals; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Hepatocellular - metabolism; Cell Cycle; Cell growth; Cell Line, Tumor; Cell Proliferation; Cell Survival; Female; Forkhead Box Protein M1 - metabolism; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Hep G2 Cells; Humans; Immunohistochemistry; Liver - metabolism; Liver Neoplasms - metabolism; Lung cancer; Male; Mice; Mice, Inbred BALB C; Microscopy, Fluorescence; Middle Aged; Research Article; Tumors; Up-Regulation; Cell proliferation; Hepatocellular carcinoma; Forkhead box M1; Cell cycle
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-015-3436-9

The Forkhead box M1 (FoxM1) transcription factor plays crucial roles in multiple biological processes, including cell proliferation, differentiation, migration, and transformation. Recent studies have reported that aberrant expression of FoxM1 was found in a variety of human cancers. However, the expression pattern of FoxM1 and its clinical significance in human hepatocellular carcinoma (HCC) have not been well characterized to date. In this study, the expression of FoxM1 was evaluated in 46 pairs of human HCC, the adjacent non-tumorous liver tissues, and 12 pairs of normal liver tissues by immumohistochemistry. FoxM1 expression was upregulated in the HCC (76.09 %) compared with non-tumorous liver tissues (39.13 %) and normal liver tissues (8.33 %) ( P  < 0.05). FoxM1 expression was significantly associated with tumor stage, tumor size, tumor number, integrality of tumor encapsulation, tumor thrombus, and AFP level ( P  < 0.05). Functionally, enforced expression of FoxM1 in HCC cell line (HHCC) remarkably enhanced cell proliferation in vitro and in vivo. Further analysis of cell cycle-related molecules showed that FoxM1 overexpression increased expressions of cyclin B1 and cyclin D1 but reduced expressions of p27 Kip1 and p21 Cip1 . Our findings suggest that FoxM1 overexpression promotes HCC cell proliferation by cell cycle regulation, which is a potential target for hepatocellular carcinoma therapy.