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Abnormal expression of HMGB-3 is significantly associated with malignant transformation of hepatocytes
AIM: To explore the relationship between dynamic expression of high mobility group box-3 (HMGB3) and malignant transformation of hepatocytes. METHODS: Expression of HMGB family proteins were observed in rat hepatocarcinogenesis models induced with 2-acetylaminofluorene. Alterations of HMGB3 were ana...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Baishideng Publishing Group Inc
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113724/ https://www.ncbi.nlm.nih.gov/pubmed/30166860 http://dx.doi.org/10.3748/wjg.v24.i32.3650 |
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author | Zheng, Wen-Jie Yao, Min Fang, Miao Wang, Li Dong, Zhi-Zhen Yao, Deng-Fu |
author_facet | Zheng, Wen-Jie Yao, Min Fang, Miao Wang, Li Dong, Zhi-Zhen Yao, Deng-Fu |
author_sort | Zheng, Wen-Jie |
collection | PubMed |
description | AIM: To explore the relationship between dynamic expression of high mobility group box-3 (HMGB3) and malignant transformation of hepatocytes. METHODS: Expression of HMGB family proteins were observed in rat hepatocarcinogenesis models induced with 2-acetylaminofluorene. Alterations of HMGB3 were analyzed at the mRNA level by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and at the protein level by immunohistochemistry or Western blotting. HMGB3 in human liver cancer tissues were evaluated using bioinformatics databases from GEO, TCGA, and Oncomine. A specific HMGB3-shRNA was used to knock down HMGB3 expression in order to investigate its effects on proliferation and cell cycle in vitro and in vivo. RESULTS: Elevated HMGB3 levels were first reported in hepatocarcinogenesis, with increasing expression from normal liver to cancer. Bioinformatic databases showed that HMGB3 expression in hepatocellular carcinoma tissues was significantly higher than that in normal liver tissues. Higher HMGB3 expression was discovered in liver cancer cells compared with LO2 cells in vitro. According to gene set enrichment analysis, HMGB3 mRNA levels were correlated with cell cycle and DNA replication pathways. Knocking down HMGB3 by specific shRNA significantly inhibited proliferation of HepG2 cells by cell cycle arrest and downregulating DNA replication related genes (cyclin B1, FEN1, and PCNA) at the mRNA and protein level. Furthermore, silencing HMGB3 significantly inhibited xenograft tumor growth (measured by Ki67) in vivo. CONCLUSION: HMGB3 is involved in malignant transformation of hepatocytes and could be a useful biomarker for diagnosis and a potential target for therapy of liver cancer. |
format | Online Article Text |
id | pubmed-6113724 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-61137242018-08-30 Abnormal expression of HMGB-3 is significantly associated with malignant transformation of hepatocytes Zheng, Wen-Jie Yao, Min Fang, Miao Wang, Li Dong, Zhi-Zhen Yao, Deng-Fu World J Gastroenterol Basic Study AIM: To explore the relationship between dynamic expression of high mobility group box-3 (HMGB3) and malignant transformation of hepatocytes. METHODS: Expression of HMGB family proteins were observed in rat hepatocarcinogenesis models induced with 2-acetylaminofluorene. Alterations of HMGB3 were analyzed at the mRNA level by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and at the protein level by immunohistochemistry or Western blotting. HMGB3 in human liver cancer tissues were evaluated using bioinformatics databases from GEO, TCGA, and Oncomine. A specific HMGB3-shRNA was used to knock down HMGB3 expression in order to investigate its effects on proliferation and cell cycle in vitro and in vivo. RESULTS: Elevated HMGB3 levels were first reported in hepatocarcinogenesis, with increasing expression from normal liver to cancer. Bioinformatic databases showed that HMGB3 expression in hepatocellular carcinoma tissues was significantly higher than that in normal liver tissues. Higher HMGB3 expression was discovered in liver cancer cells compared with LO2 cells in vitro. According to gene set enrichment analysis, HMGB3 mRNA levels were correlated with cell cycle and DNA replication pathways. Knocking down HMGB3 by specific shRNA significantly inhibited proliferation of HepG2 cells by cell cycle arrest and downregulating DNA replication related genes (cyclin B1, FEN1, and PCNA) at the mRNA and protein level. Furthermore, silencing HMGB3 significantly inhibited xenograft tumor growth (measured by Ki67) in vivo. CONCLUSION: HMGB3 is involved in malignant transformation of hepatocytes and could be a useful biomarker for diagnosis and a potential target for therapy of liver cancer. Baishideng Publishing Group Inc 2018-08-28 2018-08-28 /pmc/articles/PMC6113724/ /pubmed/30166860 http://dx.doi.org/10.3748/wjg.v24.i32.3650 Text en ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ 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. |
spellingShingle | Basic Study Zheng, Wen-Jie Yao, Min Fang, Miao Wang, Li Dong, Zhi-Zhen Yao, Deng-Fu Abnormal expression of HMGB-3 is significantly associated with malignant transformation of hepatocytes |
title | Abnormal expression of HMGB-3 is significantly associated with malignant transformation of hepatocytes |
title_full | Abnormal expression of HMGB-3 is significantly associated with malignant transformation of hepatocytes |
title_fullStr | Abnormal expression of HMGB-3 is significantly associated with malignant transformation of hepatocytes |
title_full_unstemmed | Abnormal expression of HMGB-3 is significantly associated with malignant transformation of hepatocytes |
title_short | Abnormal expression of HMGB-3 is significantly associated with malignant transformation of hepatocytes |
title_sort | abnormal expression of hmgb-3 is significantly associated with malignant transformation of hepatocytes |
topic | Basic Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113724/ https://www.ncbi.nlm.nih.gov/pubmed/30166860 http://dx.doi.org/10.3748/wjg.v24.i32.3650 |
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