• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.11a
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• pp.39-40
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• 1993

Hepatitis B virus (HBV)is a member of the Hepadna virus family whose members share a characteristic virion structure and genome size, around 3.2kb in a paritially double-stranded form. The genome of HBV contains four overlapping open reading frames designated as P(polymerase). C(core), S(surface antigen)and X. The X gene has potential to encode 154 amino acids protein.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4509-4513
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• 2013

Chronic hepatitis B virus (HBV) infection has long been the most common cause of hepatocellular carcinoma (HCC). However, some aspects of the pathogenesis of HBV infection and genesis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) are still inconclusive. An increasing number of published studies indicate that hepatitis B virus mutations are associated with risk of HCC. These variations include, in particular, mutations in ORF S,C,X gene regions. This mini-review summarizes results of clinical studies and molecular mechanisms on the possible relations of HBV mutations with the development of hepatocellular carcinoma.

• Bulletin of the Korean Chemical Society
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• v.26 no.9
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• pp.1385-1389
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• 2005

Human hepatitis B virus (HBV) is a pathogen related to the development of liver diseases including chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). However, the efficient methods to suppress HBV replication have not been developed yet. Therefore, we have used RNA interference (RNAi) as a potential tool for the suppression of HBV replication. Here, we designed a 21 nt small intefering dsRNA (siRNA) against hepatitis B virus X (HBx) RNA with 3' overhanging ends derived from T7 promoter. It has been reported that HBV X protein plays an important role in HBV gene expression and viral replication. The suppression of HBx gene expression by the 21 nt siRNA was investigated by Northern blot analysis and chloramphenicol acetyl transferase (CAT) assay. The level of HBx mRNA was decreased by siRNA in a dose-dependent manner. We also found that the 21 nt siRNA inhibited the HBV replication in hepatocellular carcinoma cell.

• Proceedings of the Microbiological Society of Korea Conference
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• 1999.04a
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• pp.23-26
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• 1999

• BMB Reports
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• v.28 no.6
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• pp.509-514
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• 1995

A putative secondary structure of the mRNA for the human hepatitis B virus (HBV) X gene is proposed based on not only chemical and enzymatic determination of its single- and double-stranded regions but also selection by the computer program MFOLD for energy minimum conformation under the constraints that the experimentally determined nucleotides were forced or prohibited to base pair. An RNA of 536 nucleotides including the 461-nucleotide HBV X mRNA sequence was synthesized in vitro by the phage T7 RNA polymerase transcription. The thermally renatured transcripts were subjected to chemical modifications with dimethylsulfate and kethoxal and enzymatic hydrolysis with single strand-specific RNase T1 and double strand-specific RNase V1, separately. The sites of modification and cleavage were detected by reverse transcriptase extension of 4 different primers. Many nucleotides could be assigned with high confidence, twenty in double-stranded and thirty-seven in Single-stranded regions. These nucleotides were forced and prohibited, respectively, to base pair in running the recursive RNA folding program MFOLD. The results suggest that 6 different regions (5 within X mRNA) of 14~23 nucleotides are Single-stranded. This putative structure provides a good working model and suggests potential target sites for antisense and ribozyme inhibitors and hybridization probes for the HBV X mRNA.

• BMB Reports
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• v.55 no.5
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• pp.220-225
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• 2022

Hepatocellular carcinoma (HCC), a primary type of liver cancer, is one of the leading causes of cancer related deaths worldwide. HCC patients have poor prognosis due to intrahepatic and extrahepatic metastasis. Hepatitis B virus (HBV) infection is one of the major causes of various liver diseases including HCC. Among HBV gene products, HBV X protein (HBx) plays an important role in the development and metastasis of HCC. However, the mechanism of HCC metastasis induced by HBx has not been elucidated yet. In this study, for the first time, we report that HBx interacts with the suppressor of cytokine signaling 1 (SOCS1) which negatively controls NF-κB by degrading p65, a subunit of NF-κB. NF-κB activates the transcription of factors associated with epithelial-mesenchymal transition (EMT), a crucial cellular process associated with invasiveness and migration of cancer cells. Here, we report that HBx physically binds to SOCS1, subsequently prevents the ubiquitination of p65, activates the transcription of EMT transcription factors and enhance cell migration and invasiveness, suggesting a new mechanism of HBV-associated HCC metastasis.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.178-178
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• 1994

Hepatitis B Virus (HBV) is a DNA virus with a 3.2kb partially double-stranded genome. The life cycle of the virus involves a reverse transcription of the greater than genome length 3.5kb mRNA. This pegenomic RNA contains all the genetic information encoded by the virus and functions as an intermediate in viral replication. Tumor suppressor p53 has previously been shown to interact with the X-gene product of the HBV, which led us to hypothesize that p53 may act as a negative regulator of HBV replication and the role of the X-gene product is to overcome the p53-mediated restriction. As a first step to prove the above hypothesis, we tested whether p53 represses the propagation of HBV in in vitro replication system. By transient cotransfection of the plasmid containing a complete copy of the HBV genome and/or the plasmid encoding p53, we found that the replication of HBV is specifically blocked by wild-type p53. The levels of HBV DNA, HBs Ag and HBc/e Ag secreted in cell culture media were dramatically reduced upon coexpresion of wild-type p53 but not by the coexpression of the mutants of p53 (G154V and R273L). Furthermore, levels of RNAs originated from HBV genome were repressed more than 10 fold by the cotransfection of the p53 encoding plasmid. These results clearly states that p53 is a nesative regulator of the HBV replication. Next, to addresss the mechanism by which p53 represses the HBV replication, we performed the transient transfection experiments employing the pregenomic/core promoter-CAT(Chloramphenicol Acetyl Transferase) construct as a reporter. Cotransfection of wild-type p53 but not the mutant p53 expression plasmids repressed the CAT activity more than 8 fold. Integrating the above results, we propose that p53 represses the replication of HBV specifically by the down-regulation of the pregenomic/core promoter, which results in the reduced DNA synthesis of HBV. Currently, the mechanism by which HBV overcomes the observed p53-mediated restriction of replication is tinder investigation.

• Journal of Microbiology and Biotechnology
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• v.10 no.6
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• pp.823-828
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• 2000

The complete nucleotide sequence of hepatitis B virus DNA isolated from Korean patient serum was determined and characterized, and its phylogenetic relation was then investigated. The viral genome was 3,215 base pairs long and included four well known open reading frames (i.e. surface antigens, core antigens, X protein and DNA polymerase). The sequence of the surface antigen showed that the HBV genome under investigation, designated HBV 315, was characteristic of subtype adr. A phylogenetic analysis using the total genome sequence revealed that HBV315 was grouped into genomic group C together with isolates from Japan, China, Thailand, Polynesia, and New Caledonia. The mean percent similarity between HBV315 and other HBV isolates in genomic group C was 97.25%, and that with other genomic groups ranged from 86.16% to 91.25%. The predicted amino acid sequences of HBV315 were compared with two closely related subtype adr isolates, M38636 and D12980. The results showed that the X gene product was identical in the three strains, while there were significant amino acid sequence differences between HBV315 and M38636 in the Pre-S1 and Pre-S2 regions.

• BMB Reports
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• v.54 no.12
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• pp.614-619
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• 2021

Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC), which is a highly aggressive cancer. HBV X protein (HBx), one of four HBV gene products, plays pivotal roles in the development and metastasis of HCC. It has been reported that HBx induces liver cancer cell migration and reorganizes actin cytoskeleton, however the molecular basis for actin cytoskeleton reorganization remains obscure. In this study, we for the first time report that HBx promotes actin polymerization and liver cancer cell migration by regulating calcium modulated protein, calmodulin (CaM). HBx physically interacts with CaM to control the level of phosphorylated cofilin, an actin depolymerizing factor. Mechanistically, HBx interacts with CaM, liberates Hsp90 from its inhibitory partner CaM, and increases the activity of Hsp90, thus activating LIMK1/cofilin pathway. Interestingly, the interaction between HBx and CaM is calcium-dependent and requires the CaM binding motif on HBx. These results indicate that HBx modulates CaM which plays a regulatory role in Hsp90/LIMK1/cofilin pathway of actin reorganization, suggesting a new mechanism of HBV-induced HCC metastasis specifically derived by HBx.

• Journal of Microbiology
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• v.43 no.6
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• pp.529-536
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• 2005

Viral infection causes stress to the endoplasmic reticulum (ER). The response to endoplasmic reticulum stress, known as the unfolded protein response (UPR), is designed to eliminate misfolded proteins and allow the cell to recover. The role of hepatitis C virus (HCV) non-structural protein NS4B, a component of the HCV replicons that induce UPR, is incompletely understood. We demonstrate that HCV NS4B could induce activating transcription factor (ATF6) and inositol-requiring enzyme 1 (IRE1), to favor the HCV subreplicon and HCV viral replication. HCV NS4B activated the IRE1 pathway, as indicated by splicing of X box-binding protein (Xbp-1) mRNA. However, transcriptional activation of the XBP-1 target gene, EDEM (ER degradation-enhancing $\alpha-mannosidase-like$ protein, a protein degradation factor), was inhibited. These results imply that NS4B might induce UPR through ATF6 and IRE1-XBP1 pathways, but might also modify the outcome to benefit HCV or HCV subreplicon replication.