RNA interference targeting human integrin α6 suppresses the metastasis potential of hepatocellular carcinoma cells

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• 作者：Guannan Lv (1)
  Tianjing Lv (2)
  Shifeng Qiao (1)
  Wei Li (1)
  Weiran Gao (1)
  Xiaohui Zhao (1)
  Jikun Wang (1)
  
• 关键词：Hepatocellular carcinoma ; integrin α6 ; Short hairpin RNA ; Metastasis
• 刊名：European Journal of Medical Research
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：18
• 期：1
• 全文大小：613 KB
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• 作者单位：Guannan Lv (1)
  Tianjing Lv (2)
  Shifeng Qiao (1)
  Wei Li (1)
  Weiran Gao (1)
  Xiaohui Zhao (1)
  Jikun Wang (1)
  
  1. The First Affiliated Hospital of Liaoning Medical College, Jinzhou, 121001, China
  2. Institute of Urology, Peking University First Hospital, Peking University, Beijing, 100034, China
  
• ISSN：2047-783X

文摘

Background Increased metastasis has been proved to be associated with a poor prognosis for hepatocellular carcinoma (HCC). There are higher-level expressions of integrin α6 in the tissues of HCC patients with a higher fatality rate. The aim of this study is to investigate the effect of short hairpin RNA (shRNA) silencing integrin α6 expression on the proliferation and metastasis in HCC cell lines. Methods Two human HCC cell lines, HepG2 and Bel-7402 were transfected with shRNA targeting human integrin α6. Protein and mRNA expression level were determined by western blot and real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to detect the transfected efficacy. The metastasis potential of HCC cells was evaluated by their proliferation, adhesion and invasion abilities. Cell proliferation was measured by MTT assay. Adhesion ability was measured by adhesion and spreading assays. The expression of matrix metalloproteinases (MMPs) was measured by qRT-PCR. The potential of invasion was measured by qRT-PCR and Transwell chamber assay. PI3K inhibitor LY294002 was used to explore the signal pathways of integrin α6 in HCC cells. Results Western blot and qRT-PCR detection showed that over 75% of integrin α6 expression in HCC cells was through knockdown by shRNA. Proliferation, adhesion, spreading and invasion of HepG2 and Bel-7402 cells were dramatically decreased in cells transfected with shRNA compared to the control cells. P-ERK and p-AKT were reduced by shRNA targeting integrin α6 and PI3K inhibitor LY294002. Conclusion Knockdown integrin α6 can inhibit the proliferation and metastasis of HCC cells through PI3K/ARK and MAPK/ERK signal pathways by shRNA in vitro. Integrin α6 can mediate the metastasis potential, and can be used as a candidate target for therapy in HCC resulting in improved patients-survival.