Letter to the Editor
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 27, 2020; 12(12): 1367-1371
Published online Dec 27, 2020. doi: 10.4254/wjh.v12.i12.1367
Autophagy related protein 9A increase in hepatitis B virus-associated hepatocellular carcinoma and the role in apoptosis
Ingorn Kimkong, Areerat Kunanopparat
Ingorn Kimkong, Department of Microbiology, Faculty of Science, Kasetsart University, Center for Advanced Studies in Tropical Natural Resources, National Research University – Kasetsart University, Bangkok 10900, Thailand
Areerat Kunanopparat, Department of Microbiology, Center of Excellence in Immunology and Immune Mediated Diseases, Chulalongkorn University, Bangkok 10330, Thailand
Author contributions: Kimkong I designed the research, wrote the manuscript and edited the manuscript; Kunanopparat A performed the majority of experiments and analyzed the data.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ingorn Kimkong, PhD, Associate Professor, Department of Microbiology, Faculty of Science, Kasetsart University, 50 Thanon Ngamwongwan, Lat Yao, Chatuchak, Bangkok 10900, Thailand. fsciiok@ku.ac.th
Received: July 31, 2020
Peer-review started: July 31, 2020
First decision: September 21, 2020
Revised: September 29, 2020
Accepted: October 19, 2020
Article in press: October 19, 2020
Published online: December 27, 2020
Processing time: 139 Days and 14.3 Hours
Abstract

The majority of hepatocellular carcinoma (HCC) cases are associated with the hepatitis B virus (HBV) infection. Autophagy related protein 9A (ATG9A) is a transmembrane protein required for autophagosome formation. In order to investigate the role of ATG9A in HBV-associated HCC, ATG9A protein expression was determined in tumor liver tissues and compared with adjacent nontumor tissues from HCC patients with or without HBV infection. In HBV-associated HCC tissues, ATG9A protein level was increased in tumor liver tissues, but not in cases of non-HBV HCC. Our findings suggested that ATG9A might be involved in HBV and cancer cell survival. Therefore, we aimed to analyze the function of ATG9A in HBV replication using RNA interference to evaluate the HBV DNA level using real-time PCR. In the present study, there were no significant differences between shATG9A-transfected HepG2.2.15 cells and the mock control. However, we found that silencing ATG9A affected apoptosis in HepG2.2.15 and HepG2 cell lines. Our results indicated that ATG9A might be partly involved in the survival of HCC. Thus, the inhibition of ATG9A together with other targets might be a potential drug target for HCC treatment.

Keywords: Autophagy; Hepatitis B virus; Hepatocellular carcinoma; Autophagy related protein 9A; Apoptosis; HBx

Core Tip: Autophagy related protein 9A (ATG9A) protein expression was increased in tumor liver tissues compared to adjacent nontumor tissues from hepatocellular carcinoma (HCC) patients with hepatitis B virus infection. We showed that silencing ATG9A increased cell apoptosis of HepG2.2.15 and HepG2 cells. These results suggested that ATG9A protein is involved in the survival of HCC. The inhibition of ATG9A combined with other targets might be a potential drug target for HCC treatment.