@misc{yao_wang_chen_chen_yang_wang_wu_yao_2020, 
  title={HIF-1α Promotes Hepatocellular Carcinoma Metastasis by Regulating Angiogenesis and Epithelial-Mesenchymal Transition}, 
  DOI={10.21203/rs.3.rs-105342/v1}, 
  abstractNote={<jats:title>Abstract</jats:title>
        <jats:p><jats:bold>Background: </jats:bold>Invasion and metastasis of hepatocellular carcinoma (HCC) still remain to be hard in medical society. However, little knowledge is known regarding the hypoxia impact in HCC with angiogenesis and epithelial-mesenchymal transition (EMT). The aims of this study were to explore the regulating roles of hypoxia-inducible factor-1α (HIF-1α) in angiogenesis and EMT of HCC. <jats:bold>Method: </jats:bold>The levels of HIF-1α, angiopoietin-2 (Ang-2), and vascular endothelial growth factor (VEGF) expression in a cohort of chronic liver diseases were detected by enzyme- linked immunosorbent assays, and their dynamic up-regulations were confirmed in model of rat hepatocyte malignant transformation. After HIF-1α gene transfected with specific miRNA, biological behaviors of HCC cells were analyzed by transwell or invasion assay; angiogenesis and EMT were analyzed at protein level by Western blot or at mRNA by quantitative real-time PCR. <jats:bold>Results: </jats:bold>The levels of <jats:bold>c</jats:bold>irculating HIF-1α, VEGF, and Ang-2 in the HCC group (145.6 ± 32.6 μg/L, 458.9 ± 125.3 μg/L, and 42.9 ± 5.1μg/L) were significantly higher (<jats:italic>P </jats:italic>&lt; 0.001) than those in the LC (79.5 ± 8.4 μg/L, 206.8 ± 56.8 μg/L, and 26.2 ± 6.1 μg/L) or the CH (60.1 ± 18.8 μg/L, 178.1 ± 85.4 μg/L, and 21.8 ± 6.9 μg/L) group, respectively. Dynamic up-regulations of HIF-1α and angiogenic factors have been confirmed by rat model with hepatocyte malignant transformation. There were closely positive correlations (<jats:italic>P </jats:italic>&lt; 0.001) between them of HIF-1α and VEGF or Ang-2. After HCC cells transfected with specific HIF-1α-miRNA, the levels of HIF-1α, VEGF and Ang-2 expression were significantly down-regulated, with inhibiting infiltration or migration, blockading EMT with increasing E-cadherin and decreasing of snail, twist and vimentin. <jats:bold>Conclusions: </jats:bold>HIF-1α over-expression could promote the metastasis or invasion of HCC via regulating neovascularization and EMT formation.</jats:p>}, 
  publisher={Research Square}, 
  author={Yao, Min and Wang, Li and Chen, Xiyu and Chen, Ying and Yang, Jie and Wang, Defeng and Wu, Wei and yao, dengfu}, 
  year={2020}, 
  month={Nov}
  }