Exosomal MicroRNA and Protein Profiles of Hepatitis B Virus-Related Hepatocellular Carcinoma Cells
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Published:2023-08-23
Issue:17
Volume:24
Page:13098
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Todorova Valentina K.1, Byrum Stephanie D.2ORCID, Mackintosh Samuel G.2, Jamshidi-Parsian Azemat3, Gies Allen J.2, Washam Charity L.2ORCID, Jenkins Samir V.3ORCID, Spiva Timothy4, Bowman Emily4, Reyna Nathan S.4ORCID, Griffin Robert J.3ORCID, Makhoul Issam1
Affiliation:
1. Department of Internal Medicine/Division of Hematology/Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA 2. Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA 3. Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA 4. Biology Department, Ouachita Baptist University, Arkadelphia, AR 71998, USA
Abstract
Infection with hepatitis B virus (HBV) is a main risk factor for hepatocellular carcinoma (HCC). Extracellular vesicles, such as exosomes, play an important role in tumor development and metastasis, including regulation of HBV-related HCC. In this study, we have characterized exosome microRNA and proteins released in vitro from hepatitis B virus (HBV)-related HCC cell lines SNU-423 and SNU-182 and immortalized normal hepatocyte cell lines (THLE2 and THLE3) using microRNA sequencing and mass spectrometry. Bioinformatics, including functional enrichment and network analysis, combined with survival analysis using data related to HCC in The Cancer Genome Atlas (TCGA) database, were applied to examine the prognostic significance of the results. More than 40 microRNAs and 200 proteins were significantly dysregulated (p < 0.05) in the exosomes released from HCC cells in comparison with the normal liver cells. The functional analysis of the differentially expressed exosomal miRNAs (i.e., mir-483, mir-133a, mir-34a, mir-155, mir-183, mir-182), their predicted targets, and exosomal differentially expressed proteins (i.e., POSTN, STAM, EXOC8, SNX9, COL1A2, IDH1, FN1) showed correlation with pathways associated with HBV, virus activity and invasion, exosome formation and adhesion, and exogenous protein binding. The results from this study may help in our understanding of the role of HBV infection in the development of HCC and in the development of new targets for treatment or non-invasive predictive biomarkers of HCC.
Funder
Arkansas Breast Cancer Research Program UAMS Core Facility Service Award NSF DBI Biology Integration Institute Cell Biology Education Consortium NIH NIGMS grant Winthrop P. Rockefeller Cancer Institute
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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