J Cancer 2019; 10(15):3501-3516. doi:10.7150/jca.29490

Research Paper

KIAA0101 is a novel transcriptional target of FoxM1 and is involved in the regulation of hepatocellular carcinoma microvascular invasion by regulating epithelial-mesenchymal transition

Tao Zhang1*, Jianrong Guo1*, Jian Gu1, Ke Chen1, Zheng Wang1,2, Huili Li1✉, Guobin Wang1✉, Jiliang Wang1✉

1. Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
2. Research Centre for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
*Contributed equally

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Citation:
Zhang T, Guo J, Gu J, Chen K, Wang Z, Li H, Wang G, Wang J. KIAA0101 is a novel transcriptional target of FoxM1 and is involved in the regulation of hepatocellular carcinoma microvascular invasion by regulating epithelial-mesenchymal transition. J Cancer 2019; 10(15):3501-3516. doi:10.7150/jca.29490. Available from http://www.jcancer.org/v10p3501.htm

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Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths due to tumor invasiveness, frequent intrahepatic dissemination and extrahepatic metastasis. However, the genes and signaling pathways that are involved remain incompletely understood. In this study, weighted gene coexpression network analysis (WGCNA) was performed to jointly analyze clinical information and gene expression data to identify key genes associated with clinical features. Through the bioinformatic analysis, the yellow module and microvascular invasion (MVI) were found to be highly associated (r=0.41) by Pearson's correlation analysis, and 20 hub genes were identified with both high gene significance (GS) and high module membership (MM) in the yellow module. Among these genes, FoxM1 and KIAA0101 were upregulated in HCC with MVI and were significantly positively correlated in HCC samples, indicating a novel regulatory network in HCC microvascular invasion. Moreover, in vitro experiments demonstrated that KIAA0101 is a direct target of FoxM1 and that KIAA0101 is required for the FoxM1-induced promotion of HCC cell invasion and migration. In addition, the FoxM1-KIAA0101 axis promotes HCC metastasis by inducing epithelial-mesenchymal transition (EMT). In summary, KIAA0101 is a novel target of FoxM1 and contributes to HCC metastasis by activating EMT. The FoxM1-KIAA0101 axis might be applied as a potential prognostic biomarker and therapeutic target for HCC.

Keywords: weighted gene coexpression network analysis, hepatocellular carcinoma, microvascular invasion, FoxM1, KIAA0101, epithelial-mesenchymal transition.