Wei XC, Xia YR, Zhou P, Xue X, Ding S, Liu LJ, Zhu F. Hepatitis B core antigen modulates exosomal miR-135a to target vesicle-associated membrane protein 2 promoting chemoresistance in hepatocellular carcinoma. World J Gastroenterol 2021; 27(48): 8302-8322 [PMID: 35068871 DOI: 10.3748/wjg.v27.i48.8302]
Corresponding Author of This Article
Fan Zhu, PhD, Professor, State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, Department of Medical Microbiology, School of Medicine, Wuhan University, No. 185 Donghu Road, Wuhan 430071, Hubei Province, China. fanzhu@whu.edu.cn
Research Domain of This Article
Oncology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
World J Gastroenterol. Dec 28, 2021; 27(48): 8302-8322 Published online Dec 28, 2021. doi: 10.3748/wjg.v27.i48.8302
Hepatitis B core antigen modulates exosomal miR-135a to target vesicle-associated membrane protein 2 promoting chemoresistance in hepatocellular carcinoma
Xiao-Cui Wei, Ya-Ru Xia, Ping Zhou, Xing Xue, Shuang Ding, Li-Juan Liu, Fan Zhu, State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan 430071, Hubei Province, China
Author contributions: Zhu F conceived the study, was in charge of overall direction and planning, and revised the manuscript; Wei XC designed and performed the experiments, and wrote the paper; Wei XC and Liu LJ revised the manuscript; Xia YR and Zhou P participated in data collection; Xue X was responsible for bioinformatics data; Ding S, and Liu LJ analyzed data; all authors read and approved the final manuscript and agreed to be accountable for all aspects of the report.
Supported byNational Natural Science Foundation of China, No. 81971943 and 81772196; and the Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University, No. TFJC 2018002.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Wuhan University, School of Basic Medical Sciences, and the study was carried out following The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans. Informed consent was obtained for experimentation with human subjects, and their privacy rights were consistently observed.
Conflict-of-interest statement: The authors hereby declare that no conflict of interest exists.
Data sharing statement: Datasets available from the corresponding author upon request.
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: Fan Zhu, PhD, Professor, State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, Department of Medical Microbiology, School of Medicine, Wuhan University, No. 185 Donghu Road, Wuhan 430071, Hubei Province, China. fanzhu@whu.edu.cn
Received: April 27, 2021 Peer-review started: April 27, 2021 First decision: June 13, 2021 Revised: June 22, 2021 Accepted: November 11, 2021 Article in press: December 11, 2021 Published online: December 28, 2021 Processing time: 240 Days and 22.7 Hours
ARTICLE HIGHLIGHTS
Research background
Hepatocellular carcinoma (HCC) is a frequently diagnosed malignant tumor caused by its main risk factor, hepatitis B virus (HBV) infection. HBV infection alters the level of miRNA in cells, which can be delivered to surrounding cells by exosomes to affect disease progression.
Research motivation
HCC is a common malignant tumor with relatively insipid early symptoms, rapid disease progression, burdensome treatment, and poor prognosis. Since HBV infection is still one of the major causes of HCC in China, the mechanism of HBV in HCC resistance remains unclear.
Research objectives
To explore the role of hepatitis B core antigen (HBc) on Dox-induced HCC resistance and the underlying mechanism.
Research methods
Exosomes were isolated by ultracentrifugation. The miRNAs differentially expressed in HCC were identified using the Cancer Genome Atlas (TCGA) database. The level of miR-135a-5p in patient tissues and exosomes was detected by quantitative polymerase chain reaction. After transfection with the indicated plasmids, cell functions affected by the HBV-regulated miR-135a/vesicle-associated membrane protein 2 (VAMP2) axis were assessed by flow cytometry and cell counting kit 8 assay.
Research results
miR-135a-5p expression was upregulated in HCC tissues and cells. HBc increased the expression of exosomal miR-135a-5p. VAMP2 is one of the potential target genes of miR-135a-5p, and functional assays showed that HBc mediated the miR-135a/VAMP2 axis to induce apoptosis protection, cell proliferation, and chemotherapy resistance in HCC.
Research conclusions
HBc elevated the expression of exosomal miR-135a-5p and promoted anti-apoptosis, cell proliferation, and chemical resistance through miR-135a-5p/VAMP2 in HCC.
Research perspectives
The role of the miR-135a-5p/VAMP2 regulatory axis in chemotherapy resistance of HCC may serve as a potential molecular therapeutic target for HCC.
