|RNA interference targeting human integrin alpha 6 suppresses the metastasis potential of hepatocellular carcinoma cells|
|Lv, Guannan1; Lv, Tianjing2; Qiao, Shifeng1; Li, Wei1; Gao, Weiran1; Zhao, Xiaohui1; Wang, Jikun1|
|关键词||Hepatocellular Carcinoma Integrin Alpha 6 Short Hairpin Rna Metastasis|
|刊名||EUROPEAN JOURNAL OF MEDICAL RESEARCH|
|WOS标题词||Science & Technology|
|类目[WOS]||Medicine, Research & Experimental|
|研究领域[WOS]||Research & Experimental Medicine|
|关键词[WOS]||CANCER ; INVASION ; PATHWAY ; ALPHA-3-BETA-1 ; ACTIVATION ; EXPRESSION ; MIGRATION ; KINASE ; MATRIX|
Background: Increased metastasis has been proved to be associated with a poor prognosis for hepatocellular carcinoma (HCC). There are higher-level expressions of integrin alpha 6 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 alpha 6 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 alpha 6. 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 alpha 6 in HCC cells.
Results: Western blot and qRT-PCR detection showed that over 75% of integrin alpha 6 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 alpha 6 and PI3K inhibitor LY294002.
Conclusion: Knockdown integrin alpha 6 can inhibit the proliferation and metastasis of HCC cells through PI3K/ARK and MAPK/ERK signal pathways by shRNA in vitro. Integrin alpha 6 can mediate the metastasis potential, and can be used as a candidate target for therapy in HCC resulting in improved patients′ survival.
|资助机构||Department of Education, Liaoning Province, China|
|作者单位||1.Liaoning Med Coll, Affiliated Hosp 1, Jinzhou 121001, Peoples R China|
2.Peking Univ, Peking Univ Hosp 1, Inst Urol, Beijing 100034, Peoples R China
|Lv, Guannan,Lv, Tianjing,Qiao, Shifeng,et al. RNA interference targeting human integrin alpha 6 suppresses the metastasis potential of hepatocellular carcinoma cells[J]. EUROPEAN JOURNAL OF MEDICAL RESEARCH,2013,18.|
|APA||Lv, Guannan.,Lv, Tianjing.,Qiao, Shifeng.,Li, Wei.,Gao, Weiran.,...&Wang, Jikun.(2013).RNA interference targeting human integrin alpha 6 suppresses the metastasis potential of hepatocellular carcinoma cells.EUROPEAN JOURNAL OF MEDICAL RESEARCH,18.|
|MLA||Lv, Guannan,et al."RNA interference targeting human integrin alpha 6 suppresses the metastasis potential of hepatocellular carcinoma cells".EUROPEAN JOURNAL OF MEDICAL RESEARCH 18(2013).|