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...
Main Authors: | , , , , , , , , |
---|---|
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 |