Department of Radiology, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China; State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi'an, China; State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi'an, China.
State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi'an, China.
Biochem Biophys Res Commun. 2018 Jun 12;500(4):924-929. doi: 10.1016/j.bbrc.2018.04.201. Epub 2018 Apr 30.
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.
转录因子叉头框蛋白 M1（FOXM1）在癌症的发生和发展中起着关键作用，包括人肝细胞癌（HCC）。然而，FOXM1 的调节作用和潜在机制仍然有限。在这里，我们发现 FOXM1 和 CCNB1 的高表达与 HCC 患者的预后不良密切相关。FOXM1 和 CCNB1 在肝肿瘤组织中同时过表达。FOXM1 的敲低显著抑制了 HCC 细胞系中 CCNB1 的表达水平，无论是在 mRNA 还是蛋白水平。机制研究表明，FOXM1 直接结合 CCNB1 的启动子区域，并在转录水平上调节 CCNB1 基因的表达水平。此外，功能丧失和挽救实验表明，CCNB1 是 FOXM1 驱动 HCC 细胞增殖所必需的。在本研究中，我们的结果部分解释了 FOXM1 的失调表达通过转录激活 CCNB1 的表达在人肝细胞癌细胞增殖中起着重要作用。这也突出了 FOXM1/CCNB1 轴可能是治疗 HCC 的一个潜在靶点。
