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RNAi Knockdown of Hypoxia-Inducible Factor-1α Decreased the Proliferation, Migration, and Invasion of Hypoxic Hepatocellular Carcinoma Cells

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Abstract

The obstruction of hepatic arterial blood flow results in tumor tissue hypoxia and elevated expression of hypoxia-inducible factor-1alpha (HIF-1α). Our study evaluated whether lentivirus-mediated short interference RNA against HIF-1α inhibits proliferation, invasion, and migration of hepatocellular carcinoma (HCC) cells under hypoxia. RNA interference knockdown of HIF-1α was achieved by HIF-1α-directed lentiviral shRNA, in a rat HCC cell line cultured under hypoxia condition for varying length of times. The expression levels of HIF-1α and vascular endothelial growth factor were examined using reverse transcription polymerase chain reaction and western blot analyses. Cell proliferation, migration, and invasion were measured by cell viability, transwell migration, and invasion assays, respectively. Inhibition of HIF-1α expression by shRNA suppressed vascular endothelial growth factor mRNA and protein levels under both normoxia and hypoxia. It also suppressed cell migration and invasion, which were enhanced under hypoxic conditions. RNAi knockdown of HIF-1α further suppressed hypoxia-mediated inhibition of the cell proliferation. These data suggest that shRNA of HIF-1α could antagonize the hypoxia-mediated increase in hepatic cancer cell migration and invasion, and synergize with hypoxia to inhibit the cell proliferation in HCC cells.

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Authors and Affiliations

  1. Department of Interventional Radiology, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai, 200032, China

    ChengShi Chen, Rong Liu, JianHua Wang, ZhiPing Yan, Sheng Qian & Wei Zhang

  2. Department of Radiology, Henan Cancer Hospital, Zhengzhou University, No.127 Dongming Road, Zhengzhou, 450008, China

    ChengShi Chen

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  1. ChengShi Chen
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  2. Rong Liu
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  3. JianHua Wang
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  6. Wei Zhang
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Correspondence to Rong Liu or JianHua Wang.

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Chen, C., Liu, R., Wang, J. et al. RNAi Knockdown of Hypoxia-Inducible Factor-1α Decreased the Proliferation, Migration, and Invasion of Hypoxic Hepatocellular Carcinoma Cells. Cell Biochem Biophys 71, 1677–1684 (2015). https://doi.org/10.1007/s12013-014-0390-x

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