CA10 is associated with HBV-related hepatocarcinogenesis

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

doi:10.1016/j.bbrep.2022.101303

CA10 is associated with HBV-related hepatocarcinogenesis

Biochem Biophys Rep. 2022 Jul 1:31:101303. doi: 10.1016/j.bbrep.2022.101303. eCollection 2022 Sep.

Authors

Kuei-Min Chung^{1

2}, Ya-Ting Chen¹, Chih-Chen Hong^{1

2}, Il-Chi Chang¹, Si-Ying Lin¹, Li-Yu Liang¹, Yi-Rong Chen¹, Chau-Ting Yeh², Shiu-Feng Huang^{1

3

4}

Affiliations

¹ Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan.
² Liver Research Unit, Linko Chang Gung Memorial Hospital, Chang-Gung University, Taoyuan, Taiwan.
³ Department of Anatomic Pathology, Linko Chang Gung Memorial Hospital, Chang-Gung University, Taoyuan, Taiwan.
⁴ Department of Anatomical Pathology, Chung-Shan Medical University Hospital, Taichung, Taiwan.

Abstract

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.

Keywords: Bad, BCL2-antagonist of cell death gene; Bcl-2, B-cell lymphoma 2 gene; Bcl-XL, B-cell lymphoma-extra large gene; CA10; CA10, Carbonic Anhydrase X; HBS, HBV surface gene; HBV; HBV, hepatitis B virus; HCC; HCC, hepatocellular carcinoma; Mcl-1, myeloid cell leukemia 1 gene; W182 nonsense mutation; miR-27b; sW182*, HBS gene with W182 nonsense mutation.