CA10 is associated with HBV-related hepatocarcinogenesis

Hepatocellular carcinoma (HCC) is the main threat for the patients infected with hepatitis B virus (HBV), but the oncogenic mechanism of HBV-related HCC is still controversial. Previously, we have found that several HBV surface gene (HBS) non-sense mutations are oncogenic. Among these mutations, sW1...

Full description

Bibliographic Details
Main Authors: Kuei-Min Chung, Ya-Ting Chen, Chih-Chen Hong, Il-Chi Chang, Si-Ying Lin, Li-Yu Liang, Yi-Rong Chen, Chau-Ting Yeh, Shiu-Feng Huang
Format: Article
Language:English
Published: Elsevier 2022-09-01
Series:Biochemistry and Biophysics Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405580822001030
_version_ 1798036695632838656
author Kuei-Min Chung
Ya-Ting Chen
Chih-Chen Hong
Il-Chi Chang
Si-Ying Lin
Li-Yu Liang
Yi-Rong Chen
Chau-Ting Yeh
Shiu-Feng Huang
author_facet Kuei-Min Chung
Ya-Ting Chen
Chih-Chen Hong
Il-Chi Chang
Si-Ying Lin
Li-Yu Liang
Yi-Rong Chen
Chau-Ting Yeh
Shiu-Feng Huang
author_sort Kuei-Min Chung
collection DOAJ
description Hepatocellular carcinoma (HCC) is the main threat for the patients infected with hepatitis B virus (HBV), but the oncogenic mechanism of HBV-related HCC is still controversial. Previously, we have found that several HBV surface gene (HBS) non-sense mutations are oncogenic. Among these mutations, sW182* was found to have the most potent oncogenicity. In this study, we found that Carbonic Anhydrase X (CA10) level was specifically increased in sW182* mutant-expressing cells. CA10 overexpression was also associated with HBS nonsense mutation in HBV-related HCC tumor tissues. Transformation and tumorigenesis assays revealed that CA10 had significant oncogenic activity. In addition, CA10 overexpression resulted in dysregulation of apoptosis-related proteins, including Mcl-1, Bcl-2, Bcl-xL and Bad. While searching for the regulatory mechanism of CA10, miR-27b was found to downregulate CA10 expression by regulating its mRNA degradation and its expression was decreased in sW182* mutant cells. Moreover, CA10 overexpression was associated with down-regulation of miR-27b in human HBV-related HCC tumor tissues with sW182* mutation. Therefore, induction of the expression of CA10 through repression of miR-27b by sW182* might be one mechanism involved in HBS mutation-related hepatocarcinogenesis.
first_indexed 2024-04-11T21:16:29Z
format Article
id doaj.art-3323f4ea14ca48028794cf0c9efb7f72
institution Directory Open Access Journal
issn 2405-5808
language English
last_indexed 2024-04-11T21:16:29Z
publishDate 2022-09-01
publisher Elsevier
record_format Article
series Biochemistry and Biophysics Reports
spelling doaj.art-3323f4ea14ca48028794cf0c9efb7f722022-12-22T04:02:47ZengElsevierBiochemistry and Biophysics Reports2405-58082022-09-0131101303CA10 is associated with HBV-related hepatocarcinogenesisKuei-Min Chung0Ya-Ting Chen1Chih-Chen Hong2Il-Chi Chang3Si-Ying Lin4Li-Yu Liang5Yi-Rong Chen6Chau-Ting Yeh7Shiu-Feng Huang8Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan; Liver Research Unit, Linko Chang Gung Memorial Hospital, Chang-Gung University, Taoyuan, TaiwanInstitute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, TaiwanInstitute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan; Liver Research Unit, Linko Chang Gung Memorial Hospital, Chang-Gung University, Taoyuan, TaiwanInstitute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, TaiwanInstitute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, TaiwanInstitute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, TaiwanInstitute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, TaiwanLiver Research Unit, Linko Chang Gung Memorial Hospital, Chang-Gung University, Taoyuan, TaiwanInstitute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan; Department of Anatomic Pathology, Linko Chang Gung Memorial Hospital, Chang-Gung University, Taoyuan, Taiwan; Department of Anatomical Pathology, Chung-Shan Medical University Hospital, Taichung, Taiwan; Corresponding author. Institute of Molecular and Genomic Medicine, National Health Research Institutes, 35, Keyan Road, Zhunan Town, Miaoli County, 350, Taiwan.Hepatocellular carcinoma (HCC) is the main threat for the patients infected with hepatitis B virus (HBV), but the oncogenic mechanism of HBV-related HCC is still controversial. Previously, we have found that several HBV surface gene (HBS) non-sense mutations are oncogenic. Among these mutations, sW182* was found to have the most potent oncogenicity. In this study, we found that Carbonic Anhydrase X (CA10) level was specifically increased in sW182* mutant-expressing cells. CA10 overexpression was also associated with HBS nonsense mutation in HBV-related HCC tumor tissues. Transformation and tumorigenesis assays revealed that CA10 had significant oncogenic activity. In addition, CA10 overexpression resulted in dysregulation of apoptosis-related proteins, including Mcl-1, Bcl-2, Bcl-xL and Bad. While searching for the regulatory mechanism of CA10, miR-27b was found to downregulate CA10 expression by regulating its mRNA degradation and its expression was decreased in sW182* mutant cells. Moreover, CA10 overexpression was associated with down-regulation of miR-27b in human HBV-related HCC tumor tissues with sW182* mutation. Therefore, induction of the expression of CA10 through repression of miR-27b by sW182* might be one mechanism involved in HBS mutation-related hepatocarcinogenesis.http://www.sciencedirect.com/science/article/pii/S2405580822001030CA10HCCW182 nonsense mutationmiR-27bHBV
spellingShingle Kuei-Min Chung
Ya-Ting Chen
Chih-Chen Hong
Il-Chi Chang
Si-Ying Lin
Li-Yu Liang
Yi-Rong Chen
Chau-Ting Yeh
Shiu-Feng Huang
CA10 is associated with HBV-related hepatocarcinogenesis
Biochemistry and Biophysics Reports
CA10
HCC
W182 nonsense mutation
miR-27b
HBV
title CA10 is associated with HBV-related hepatocarcinogenesis
title_full CA10 is associated with HBV-related hepatocarcinogenesis
title_fullStr CA10 is associated with HBV-related hepatocarcinogenesis
title_full_unstemmed CA10 is associated with HBV-related hepatocarcinogenesis
title_short CA10 is associated with HBV-related hepatocarcinogenesis
title_sort ca10 is associated with hbv related hepatocarcinogenesis
topic CA10
HCC
W182 nonsense mutation
miR-27b
HBV
url http://www.sciencedirect.com/science/article/pii/S2405580822001030
work_keys_str_mv AT kueiminchung ca10isassociatedwithhbvrelatedhepatocarcinogenesis
AT yatingchen ca10isassociatedwithhbvrelatedhepatocarcinogenesis
AT chihchenhong ca10isassociatedwithhbvrelatedhepatocarcinogenesis
AT ilchichang ca10isassociatedwithhbvrelatedhepatocarcinogenesis
AT siyinglin ca10isassociatedwithhbvrelatedhepatocarcinogenesis
AT liyuliang ca10isassociatedwithhbvrelatedhepatocarcinogenesis
AT yirongchen ca10isassociatedwithhbvrelatedhepatocarcinogenesis
AT chautingyeh ca10isassociatedwithhbvrelatedhepatocarcinogenesis
AT shiufenghuang ca10isassociatedwithhbvrelatedhepatocarcinogenesis