HEPATITIS & LIVER DISEASES

Biography

Kanghong Hu obtained his Ph.D. in Molecular Virology at the University of Düsseldorf, Germany in 1999. Having 7 year Post-doctor fellow career at the University of Düsseldorf and at the University Hospital of Freiburg i. Br., Dr. Hu had been senior scientist in the Institute of Molecular and Cellular Anatomy, University of Regensburg, Germany since 2006. He performed study on viral RNA structure/function relationship and built his team as a Principal Investigator in Wuhan Institute of Virology, CAS in 2008 and has been the Director, Sino-German Biomedical Center at Hubei University of Technology since 2014. His major interests are to explore the underlying replication mechanisms of hepatitis B virus (HBV), the progression of liver fibrosis and the development of hepatocyte carcinoma. He published so far 47 peer-reviewed SCI papers and had 23 international and Chinese Patents being granted.

Abstract

Background: Chronic hepatitis B virus (HBV) infected patients have an almost 100-fold increased risk to develop hepatocellular carcinoma (HCC). However, the understanding of the underlying mechanism of HBV-related HCC remains poor. In our previous study, the block of proliferation 1 (BOP1) and the phosphatidylethanolamine-binding protein 4 (PEBP4) were screened out as potential hub genes for the HBV-related HCC through a weighted gene co-expression network analysis (WGCNA)-based bioinformatics algorithm. In this study, we further investigated the both genes for their correlation with the progression of HCC.

Methods: We explored the biological significance of BOP1 and PEBP4 with over-expression and down-regulation analyses both in vivo and in vitro. The mRNA and expression levels of BOP1 and of PEBP4 in 5 HBV-related HCC patient tissues were measured with quantitative real-time PCR (qRT-PCR) and western blotting, respectively. The relationship between BOP1 or PEBP4 with PI3K/Akt pathway was also investigated by western blotting.

Results: An up-regulation of BOP1 and PEBP4 was observed in tumor tissues compared to their adjacent normal tissues. The same results were obtained in 2 HCC cell lines, HepG2 and Huh7, compared to the normal liver cell line, HL7702. Functionally, the increased BOP1 and PEBP4 expression levels through plasmid transfection into HepG2 promoted the cell proliferation and migration, while the knockdown of expression levels of BOP1 and PEBP4 through shRNA silencing in HepG2 suppressed the cell proliferation and migration and promoted the cell apoptosis. Moreover, the increased BOP1 and PEBP4 level may promote the tumorgenesis and the progression of HCC through activating the phosphorylation of PI3K and Akt and subsequently affecting the PI3K/Akt pathway.

Conclusion: Our findings revealed that BOP1 and PEBP4 are tumor-promoting genes and may represent potential biomarkers or therapeutic targets for HCC.