DNA methyltransferase inhibitor assay system based on the HBx-induced DNA methylation of E-cadherin

Lee, Hyehyeon; Sohn, Jin Bae; Kim, Soo Shin; Jang, Kyung Lib

doi:10.1016/j.bbrc.2013.07.094

Cited by 5 publications

(3 citation statements)

References 34 publications

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“…Then, we found that HBx inhibits the expression of GAS5 and promotes the viability and invasion of HCC cells by inhibiting GAS5 expression. HBx is closely related to DNA methylation through interaction with DNMTs (Lee et al 2013; Wei et al 2013). In the present study, we revealed that the methylation level of GAS5 is increased in HBx‐overexpressing HCC cells.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B virus x gene-downregulated growth-arrest specific 5 inhibits the cell viability and invasion of hepatocellular carcinoma cell lines by activating Y-box-binding protein 1/p21 signaling

Hou

et al. 2021

J. Cell Commun. Signal.

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The long noncoding RNA growth-arrest specific 5 (GAS5) is a suppressor of many cancers. However, the role and mechanism of action of GAS5 in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unclear. Here, the expression of hepatitis B virus x gene (HBx) mRNA and GAS5 was assessed by qRT-PCR, and western blot analysis was performed to determine the protein expression levels. In addition, the cell viability and invasion of cells were confirmed using MTT assay and Transwell assay, respectively. The DNA methylation level of GAS5 was measured by methylation-specific PCR. Moreover, RIP assay and RNA pull down assay were carried out to examine the combination of Y-box-binding protein 1 (YBX1) and GAS5. First, our data proved that HBx is increased, while GAS5 is decreased in HCC cell lines. Subsequently, we found that HBx facilitates HCC cell viability and invasion by inhibiting GAS5 expression. Then, we further clarified that HBx induces the DNA methylation of GAS5 by promoting methyltransferase expression, thereby suppressing GAS5 expression. Furthermore, GAS5 binds YBX1 and promotes YBX1 and p21 expression. Finally, the functional analysis revealed that the upregulation of GAS5 could attenuate cell viability and invasion by boosting p21 expression via binding YBX1. Overall, our results demonstrated that HBx promotes HCC progression by inducing GAS5 methylation to reduce its expression. The upregulation of GAS5 suppressed HBV-related HCC by activating YBX1/p21 signaling. Our data provide novel evidence supporting the potential of GAS5 as a treatment target in HBV-related HCC.

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Section: Discussionmentioning

confidence: 99%

Hepatitis B virus x gene-downregulated growth-arrest specific 5 inhibits the cell viability and invasion of hepatocellular carcinoma cell lines by activating Y-box-binding protein 1/p21 signaling

Hou

et al. 2021

J. Cell Commun. Signal.

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“…Some studies found that hepatitis B virus X protein (HBx) could play a crucial role in epigenetic tumorigenesis of HBV-related HCC [30][31][32]. HBx could increase the expressions of DNA-methyltransferase1 (DNMT1) and DNMT3b to induce hypermethylation of tumor suppressor genes [28,[33][34][35]. DNA hypermethylation could silence the expressions of TSGs and lead to hepatocarcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Association between gene methylation and HBV infection in hepatocellular carcinoma: A meta-analysis

Zhang¹,

Huang²,

Sui³

et al. 2019

J. Cancer

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Gene methylation is an epigenetic alteration in hepatocellular carcinoma (HCC), and hepatitis B virus (HBV) plays a crucial role in carcinogenesis of HCC. However, the association between gene methylation and HBV infection in HCC remains unclear. In our study, we conducted a comprehensive meta-analysis to evaluate the association. A total of 1,148 studies were initially retrieved from some literature database. After a four-step filtration, we obtained 69 case-control studies in this meta-analysis. Our results showed six genes (p16, RASSF1A, GSTP1, APC, p15 and SFRP1) in HBV-positive carcinoma tissues, one gene (GSTP1) in HBV-positive adjacent tissues and two gene (p16 and APC) in HBV-positive carcinoma serums, which were significantly hypermethylated. Subgroup meta-analysis by geographical populations revealed that GSTP1 methylation was significantly higher in HBV-positive carcinoma tissues in China and Japan. In addition, p16 and RASSF1A methylation was significantly higher in China but not in Japan. Our study indicated that HBV infection could induce DNA methylation in HCC and DNA methylation could lead to the development of HBV-related HCC.

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“…E-cadherin expression is frequently altered in HCC [ 27 , 28 ], particularly in HBV-related tumors [ 28 , 29 ]. The HBx protein represses E-cadherin expression by activating DNA methyltransferase 1 [ 30 , 31 ]. The results of the present study show that HBx increased HCCR expression and that HCCR, in turn, suppressed E-cadherin expression, suggesting that HCCR may also be involved in the mechanism of HBx regulation E-cadherin.…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of human cervical cancer proto-oncogene contributes to hepatitis B virus-induced malignant transformation of hepatocyte by down-regulating E-cadherin

Dai

Zhang

et al. 2015

Oncotarget

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Hepatocellular carcinoma (HCC) is one of the most fatal human malignancies, Human cervical cancer proto-oncogene (HCCR) aberrantly expressed in a number of malignant tumors, including HCC. HCC is associated with Hepatitis B virus (HBV) infection in a large percentage of cases. To explore the regulation and function of HCCR expression in the development of HCC, we detected HCCR expression in HBV expressing hepatocytes. Results showed that the expression of HCCR was higher in HBV-expressing hepatocytes than that in control cells. Examining different components of HBV revealed that the HBx promotes HCCR expression in hepatocytes via the T-cell factor (TCF)/β-catenin pathway. HCCR expression in HBx transgenic mice increased with as the mice aged and developed tumors. We also found that overexpression of HCCR in hepatocytes promoted cell proliferation, migration, and invasion and reduced cell adhesion. Suppressing HCCR expression abolished the effect of HBx-induced hepatocyte growth. In addition, HCCR represses the expression of E-cadherin by inhibition its promoter activity, which might correlate with the effects of HCCR in hepatocytes. Taken together, these results demonstrate that HBx-HCCR-E-cadherin regulation pathway might play an important role in HBV-induced hepatocarcinogenesis. They also imply that HCCR is a potential risk marker for HCC and/or a potential therapeutic target.

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DNA methyltransferase inhibitor assay system based on the HBx-induced DNA methylation of E-cadherin

Cited by 5 publications

References 34 publications

Hepatitis B virus x gene-downregulated growth-arrest specific 5 inhibits the cell viability and invasion of hepatocellular carcinoma cell lines by activating Y-box-binding protein 1/p21 signaling

Hepatitis B virus x gene-downregulated growth-arrest specific 5 inhibits the cell viability and invasion of hepatocellular carcinoma cell lines by activating Y-box-binding protein 1/p21 signaling

Association between gene methylation and HBV infection in hepatocellular carcinoma: A meta-analysis

Up-regulation of human cervical cancer proto-oncogene contributes to hepatitis B virus-induced malignant transformation of hepatocyte by down-regulating E-cadherin

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