Autophagy Related-Protein 16-1 Up-Regulated in Hepatitis B Virus-Related Hepatocellular Carcinoma and Impaired Apoptosis.

Abstract

BackgroundHepatocellular carcinoma (HCC) as primary malignancy of the liver has become the most common type of cancer worldwide. HCC development is mainly caused by viruses, especially the hepatitis B virus (HBV). Autophagy is an important defense mechanism against virus infection; however, HBV promotes autophagy mediated by the HBx protein which stimulates its replication. The autophagy-related protein 16-1 (ATG16L1) binds to the ATG12-ATG5 conjugate and forms a large protein autophagosome complex. Previous studies indicated that the ATG12-ATG5 conjugate was involved in HBV-associated HCC. Therefore, the ATG16L1 protein might consistently relate to this condition.MethodsAccordingly, the ATG16L1 protein expression was determined in tumor and non-tumor liver cell lines and liver tissue samples using immunoblotting, and also investigated in ATG16L1-knockdown cells to further clarify this function.ResultsOur results showed that the ATG16L1 protein was up-regulated in HepG2.2.15 and HepG2 cell lines compared to THLE-2 cells. This protein also increased in tumor liver tissues of HCC patients with HBV infection compared to adjacent non-tumor tissues. Silenced-ATG16L1 also significantly promoted apoptosis in HepG2 cells cultured in starvation conditions.ConclusionsFindings suggested ATG16L1 as an important molecule involved in apoptosis processes for HCC cells. A more profound understanding is required regarding the mechanisms that link autophagy and apoptosis in HCC development.