KIAA0101 is a novel transcriptional target of FoxM1 and is involved in the regulation of hepatocellular carcinoma microvascular invasion by regulating epithelial-mesenchymal transition
Autor: | Jiliang Wang, Jian Gu, Huili Li, Guobin Wang, Jianrong Guo, Zheng Wang, Tao Zhang, Ke Chen |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
microvascular invasion Biology Metastasis weighted gene coexpression network analysis 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Gene expression medicine Epithelial–mesenchymal transition Gene hepatocellular carcinoma KIAA0101 medicine.disease digestive system diseases 030104 developmental biology Oncology 030220 oncology & carcinogenesis Hepatocellular carcinoma FoxM1 Cancer research FOXM1 Signal transduction epithelial-mesenchymal transition Research Paper |
Zdroj: | Journal of Cancer |
ISSN: | 1837-9664 |
Popis: | 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. |
Databáze: | OpenAIRE |
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