Peantum Jiaranai, Kunanopparat Areerat, Hirankarn Nattiya, Tangkijvanich Pisit, Kimkong Ingorn
Department of Microbiology, Faculty of Science, Kasetsart University, Bangkok, Thailand.
Center of Excellence in Immunology and Immune Mediated Diseases, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Gastroenterology Res. 2018 Dec;11(6):404-410. doi: 10.14740/gr1075w. Epub 2018 Dec 17.
Hepatocellular 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.
Accordingly, 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.
Our 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.
Findings 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.
肝细胞癌（HCC）作为肝脏的原发性恶性肿瘤，已成为全球最常见的癌症类型。HCC的发生主要由病毒引起，尤其是乙型肝炎病毒（HBV）。自噬是一种重要的抗病毒感染防御机制；然而，HBV通过刺激其复制的HBx蛋白促进自噬。自噬相关蛋白16-1（ATG16L1）与ATG12-ATG5共轭物结合并形成大型蛋白质自噬体复合物。先前的研究表明，ATG12-ATG5共轭物参与HBV相关的HCC。因此，ATG16L1蛋白可能始终与这种情况相关。
相应地，使用免疫印迹法在肿瘤和非肿瘤肝细胞系及肝组织样本中测定ATG16L1蛋白表达，并在ATG16L1敲低细胞中进行研究以进一步阐明其功能。
我们的结果表明，与THLE-2细胞相比，HepG2.2.15和HepG2细胞系中ATG16L1蛋白上调。与相邻的非肿瘤组织相比，该蛋白在HBV感染的HCC患者的肿瘤肝组织中也增加。沉默ATG16L1也显著促进了在饥饿条件下培养的HepG2细胞的凋亡。
研究结果表明ATG16L1是参与HCC细胞凋亡过程的重要分子。需要对HCC发展过程中自噬与凋亡之间的联系机制有更深入的了解。
