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Molecular Mechanism Underlying the Suppression of CPB2 Expression Caused by Persistent Hepatitis C Virus RNA Replication.
- Source :
-
Acta medica Okayama [Acta Med Okayama] 2016; Vol. 70 (2), pp. 75-88. - Publication Year :
- 2016
-
Abstract
- The mechanisms of hepatitis C virus (HCV)-associated hepatocarcinogenesis and disease progression are unclear. We previously observed that the expression level of carboxypeptidase B2 (CPB2) gene was remarkably suppressed by persistent HCV RNA replication in human hepatoma cell line Li23- derived cells. The results of the present study demonstrated that the CPB2 expression in patients with chronic hepatitis C was inversely correlated with several risk factors of hepatic fibrosis or steatosis, although ectopic CPB2 expression did not suppress the expression of fibrogenic or lipogenic genes. The suppressed CPB2 expression was restored by treatment with 5-azacytidine. To clarify the mechanism underlying this phenomenon, we analyzed the CPB2 promoter, and the results revealed that (1) hepatocyte nuclear factor 1 (HNF1), especially HNF1α, was essential for the CPB2 promoter, and (2) CPB2 promoter was not methylated by persistent HCV RNA replication. The expression levels of HNF1α and HNF1β were also not changed by persistent HCV RNA replication. These results suggest the existence of 5-azacytidine-inducible or -reducible unknown factor(s) that can control the CPB2 expression. To evaluate this idea we performed a microarray analysis, and several gene candidates corresponding to the suggested factor(s) were identified.
- Subjects :
- Azacitidine pharmacology
Carboxypeptidase B2 genetics
Cell Line, Tumor
Enzyme Inhibitors pharmacology
Gene Expression Regulation, Enzymologic drug effects
Gene Expression Regulation, Viral drug effects
Gene Knockdown Techniques
Hepatitis C pathology
Hepatitis C virology
Hepatocyte Nuclear Factor 1-alpha genetics
Hepatocyte Nuclear Factor 1-alpha metabolism
Hepatocyte Nuclear Factor 1-beta genetics
Hepatocyte Nuclear Factor 1-beta metabolism
Humans
MicroRNAs
Oligonucleotide Array Sequence Analysis
Promoter Regions, Genetic
Carboxypeptidase B2 metabolism
Hepacivirus physiology
Hepatitis C metabolism
RNA, Viral physiology
Virus Replication physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0386-300X
- Volume :
- 70
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Acta medica Okayama
- Publication Type :
- Academic Journal
- Accession number :
- 27094832
- Full Text :
- https://doi.org/10.18926/AMO/54186