upregulated microrna-29a by hepatitis b virus x protein enhances hepatoma cell migration by targeting pten in cell culture model调节microrna-29a乙肝病毒x针对pten蛋白提高肝癌细胞迁移的细胞培养模型.pdf

Upregulated MicroRNA-29a by Hepatitis B Virus X Protein Enhances Hepatoma Cell Migration by Targeting PTEN in Cell Culture Model 1 1 1 1 2 1 Guangyao Kong , Junping Zhang , Shuai Zhang , Changliang Shan , Lihong Ye *, Xiaodong Zhang * 1 Key Laboratory of Molecular Microbiology and Technology of Ministry of Education, Department of Cancer Research, Institute for Molecular Biology, College of Life Sciences, Nankai University, Tianjin, People’s Republic of China, 2 Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, People’s Republic of China Abstract Hepatitis B virus X protein (HBx) plays important roles in the development of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) contribute to cancer development by acting as oncogenes or tumor suppressors. Previously, we reported that HBx was able to promote the migration of hepatoma HepG2 cells. However, the regulation of miRNAs in the development of HBV-related HCC is poorly understood. In the present study, we reported that miR-29a was a novel regulator of migration of hepatoma cells mediated by HBx. Our data showed that the expression of miR-29a was dramatically increased in p21-HBx transgenic mice, HBx-transfected hepatoma HepG2-X (or H7402-X) cells and HepG2.2.15 cells that constitutively replicate HBV. However, our data showed that miR-29a was upregulated in 4 of the 11 clinical HCC samples. We found that the overexpression of miR-29a promoted the migration of HepG2 cells, while a specific miR-29a inhibitor could partially abolish the enhanced migration of HepG2-X cells. Moreover, we identified PTEN was one of the target genes of miR-29a in HepG2 cells. The deletion of the miR-29a-binding site was able to abolish the role of miR-29a in suppre