Epigenetic mechanisms in hepatocellular carcinoma: How environmental factors influence the epigenome

Herceg, Zdenko; Paliwal, Anupam

doi:10.1016/j.mrrev.2011.04.001

Cited by 149 publications

(120 citation statements)

References 52 publications

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“…The possible explanation is that HBx affects the expression of important cellular genes resulting from its transcriptional transactivation and transrepression properties. HBx can directly interact with the acetyltransferase p300/CBP complex in coordination to enhance the activity of CREB to promote transcription, leading to activation of the acetylated histone state of the target cellular genes (18,42). HBx recruits HDAC1 to the promoter of IGFBP-3 and induces the formation of the Sp1/HDAC1 complex, resulting in deacetylation of Sp1 and inhibition of the transcription of IGFBP-3 (43).…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B virus X protein modulates remodelling of minichromosomes related to hepatitis B virus replication in HepG2 cells

Luo

Chen

Gong

et al. 2012

International Journal of Molecular Medicine

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Abstract. Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is organised into minichromosomes by histone and non-histone proteins. Remodelling of minichromosomes is crucial for the regulation of HBV replication, which is dependent on the presence of the hepatitis B virus X protein (HBx). However, the mechanisms of HBx-dependent HBV replication remain obscure. The objective of this study was to investigate the mechanism of HBx-dependent HBV replication through the pathway of chromatin remodelling. The role of HBx was investigated by transfecting human HepG2 cells with the linear full-length HBV genome (wild-type) or HBx-deficient mutant HBV DNA (HBx mutant). Our results showed that although the formation of cccDNA was not affected by HBx, HBV replication, transcription and antigen secretion were all significantly reduced, resulting from the absence of HBx. The acetylation, mono-methylation and phosphorylation of cccDNA-bound histone H3 were associated with HBV replication. In addition, the levels of cccDNA-bound methylated, phosphorylated and acetylated histone H3 decreased sharply in HBx mutant HBV DNA. HBx modulated not only the status of acetylation but also the methylation and phosphorylation of histone H3 bound to the cccDNA during HBV replication in HepG2 cells. These findings suggest that HBx plays an important role in modulating the remodelling of minichromosomes related to HBV replication and it may regulate viral replication through the pathway of chromatin remodelling.

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Section: Discussionmentioning

confidence: 99%

Hepatitis B virus X protein modulates remodelling of minichromosomes related to hepatitis B virus replication in HepG2 cells

Luo

Chen

Gong

et al. 2012

International Journal of Molecular Medicine

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“…The occurrence of HCC is results from multiple factors, including the activation of certain oncogenes, inactivation of TSGs and exogenous stimuli. Previous studies have demonstrated that the hypermethylation of CpG islands in tumor suppressor gene (TSG) promoters is closely associated with the formation of HCC, which may transform the spatial structure of chromatin and hence block/silence the transcription of TSGs via recruiting proteins of the methyl CpG binding domain (MBD) family in addition to the associated protein complexes (1,2). Epigenetic silencing is a relatively common mechanism of TSG inactivation (3).…”

Section: Introductionmentioning

confidence: 99%

Detecting abnormal methylation of tumor suppressor genes GSTP1, P16, RIZ1, and RASSF1A in hepatocellular carcinoma and its clinical significance

Jiang

et al. 2015

Oncology Letters

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Abstract. Hepatocellular carcinoma (HCC) has a high rate of mortality. Further studies into epigenetic changes in HCC, particularly the abnormal methylation of tumor suppressor genes (TSGs), are required, since these changes may provide novel biomarkers for early screening and diagnosis of HCC. By using methylation-specific polymerase chain reaction (MSP), the present study detected the methylation status in the promoter region of 4 candidate TSGs, GSTP1, P16, RIZ1, and RASSF1A, respectively, in 35 paired HCC and tumor-adjacent liver tissues in addition to 20 normal liver tissues. Their effect on the initiation and progression of HCC was also investigated by analyzing the clinicopathological data. The results of the present study revealed that the methylation level of RIZ1 and GSTP1 genes in HCC was significantly increased compared with that in the adjacent tissues (P<0.01) and the normal liver tissues (P<0.01). The methylation frequency of P16 and RASSF1A genes was not significantly increased compared with that observed in the adjacent tissues (P>0.05) but was significantly increased compared with the normal tissues (P<0.01). In HCC tissues, the methylation frequency of the GSTP1 gene in tumors with capsular invasion was significantly increased compared with that in tumors without capsular invasion (P<0.05). The methylation frequency of P16 gene in hepatitis B surface antigen (HbsAg)-positive HCC patients was significantly increased compared with that in HbsAg-negative patients (P<0.05). The methylation status of RIZ1 and RASSF1A genes was not significantly correlated with the clinicopathological data (P>0.05). Previous studies have demonstrated that the methylation status of RIZ1 and GSTP1 genes is HCC-specific, and thus may be used as a biomarker to assist the clinical diagnosis of HCC. While the methylation of GSTP1 gene promoter may associate with the invasiveness of HCC, chronic hepatitis B virus infection may be the cause of methylation-induced P16 inactivation. IntroductionHCC is one of the tumors with the highest incidence worldwide, and its incidence and mortality in China have remained high. The occurrence of HCC is results from multiple factors, including the activation of certain oncogenes, inactivation of TSGs and exogenous stimuli. Previous studies have demonstrated that the hypermethylation of CpG islands in tumor suppressor gene (TSG) promoters is closely associated with the formation of HCC, which may transform the spatial structure of chromatin and hence block/silence the transcription of TSGs via recruiting proteins of the methyl CpG binding domain (MBD) family in addition to the associated protein complexes (1,2). Epigenetic silencing is a relatively common mechanism of TSG inactivation (3). The aberrant methylation of tumor-associated genes, particularly TSGs, requires further research.A high frequency of methylation inactivation of the GSTP1 gene has been observed in human prostate, kidney, and liver cancers (4-6). Zhang et al (7) and Tchou et al (8) demonstrated that there is a high freq...

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“…Recientes estudios de epigenética han identificado un gran número de genes y rutas que podrían estar implicadas en la evolución a carcinoma hepatocelular, en concreto se ha visto que se producen cambios en la metilación del ADN, alteraciones en las histonas y en el silenciamiento de genes mediado por ARN (Herceg y Paliwal, 2011).…”

Section: Objetivos Del Presente Trabajounclassified

Estudio de genética del virus de la hepatitis C en cultivos celulares

Ibañez

2011

Revista Complutense De Ciencias Veterinarias

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RESUMENEl virus de la hepatitis C infecta a unos 170 millones de personas en todo el mundo, dando lugar en muchos de los pacientes afectados a cirrosis y carcinoma hepatocelular.Aunque en los últimos años se ha avanzado mucho en su conocimiento gracias a que se consiguió el desarrollo y la optimización de un sistema de cultivo celular, aún hay etapas de su ciclo de replicación que no se comprenden totalmente, y muchas de las funciones de las proteínas virales aún no están claras. Con el fin de dilucidar el papel que juegan dos de estas proteínas en el desarrollo de carcinoma hepatocelular, en este trabajo se desarrolló un sistema de expresión de los genes de la proteína del core y la proteína no estructural NS5A del virus, de tres genotipos distintos, mediante la clonación de los mismos y su posterior transfección en líneas celulares de hepatoma. Se obtuvieron buenos niveles de expresión de ambas proteínas, lo que servirá como base para futuras investigaciones.Palabras clave: hepatitis C, clonación, transfección, core, NS5A. ABSTRACTThe hepatitis C virus causes infection in approximately 170 million persons worldwide, and in many of these patients the infection will progress to cirrhosis and hepatocellular carcinoma. Although there have been great advancements in the knowledge of this virus due to the development and optimization of a cell culture system during the past few years, some of the stages of the viral cycle are not completely understood, and many of the functions of the viral proteins still remain unclear. To elucidate the role of two of these

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Epigenetic mechanisms in hepatocellular carcinoma: How environmental factors influence the epigenome

Cited by 149 publications

References 52 publications

Hepatitis B virus X protein modulates remodelling of minichromosomes related to hepatitis B virus replication in HepG2 cells

Hepatitis B virus X protein modulates remodelling of minichromosomes related to hepatitis B virus replication in HepG2 cells

Detecting abnormal methylation of tumor suppressor genes GSTP1, P16, RIZ1, and RASSF1A in hepatocellular carcinoma and its clinical significance

Estudio de genética del virus de la hepatitis C en cultivos celulares

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