ArticleJournal of experimental & clinical cancer research : CR2015
Hepatitis C virus core protein modulates pRb2/p130 expression in human hepatocellular carcinoma cell lines through promoter methylation.
Article in Journal of experimental & clinical cancer research : CR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- MiR-106b-5p promotes gastric cancer progression by directly targeting the tumor suppressor RBL2.Scientific reports · 2025Article
- HCV and HCC Tango-Deciphering the Intricate Dance of Disease: A Review Article.International journal of molecular sciences · 2023Review
- Mechanisms by Which Probiotic Bacteria Attenuate the Risk of Hepatocellular Carcinoma.International journal of molecular sciences · 2021Review
- 5-AZA-dC induces epigenetic changes associated with modified glycosylation of secreted glycoproteins and increased EMT and migration in chemo-sensitive cancer cells.Clinical epigenetics · 2021Article
- Viral Causality of Human Cancer and Potential Roles of Human Endogenous Retroviruses in the Multi-Omics Era: An Evolutionary Epidemiology Review.Frontiers in oncology · 2021Review
- MHC Phosphopeptides: Promising Targets for Immunotherapy of Cancer and Other Chronic Diseases.Molecular & cellular proteomics : MCP · 2021Review
- Role of Retinoblastoma Protein Family (Rb/p105 and Rb2/p130) Expression in the Histopathological Classification of Borderline Ovarian Tumors.Frontiers in medicine · 2020Article
- Whole Genome 5'-Methylcytosine Level Quantification in Cirrhotic HCV-Infected Egyptian Patients with and without Hepatocellular Carcinoma.International journal of genomics · 2020Article
- DNA hypermethylation of aurora kinase A in hepatitis C virus‑positive hepatocellular carcinoma.Molecular medicine reports · 2019Article
- miR‑300 regulates tumor proliferation and metastasis by targeting lymphoid enhancer‑binding factor 1 in hepatocellular carcinoma.International journal of oncology · 2019Article
- USP24 induces IL-6 in tumor-associated microenvironment by stabilizing p300 and β-TrCP and promotes cancer malignancy.Nature communications · 2018Article
- Nucleosomes positioning around transcriptional start site of tumor suppressor (Rbl2/p130) gene in breast cancer.Molecular biology reports · 2018Article
- Overexpression of centromere protein K (CENP-K) gene in hepatocellular carcinoma promote cell proliferation by activating AKT/TP53 signal pathway.Oncotarget · 2017Article
- Effects of hepatitis C virus core protein and nonstructural protein 4B on the Wnt/β-catenin pathway.BMC microbiology · 2017Article
- Hepatitis C virus NS3 protein enhances hepatocellular carcinoma cell invasion by promoting PPM1A ubiquitination and degradation.Journal of experimental & clinical cancer research : CR · 2017Article
- Inhibition of EZH2 via activation of SAPK/JNK and reduction of p65 and DNMT1 as a novel mechanism in inhibition of human lung cancer cells by polyphyllin I.Journal of experimental & clinical cancer research : CR · 2016Article
- MiR-130a-3p regulates cell migration and invasion via inhibition of Smad4 in gemcitabine resistant hepatoma cells.Journal of experimental & clinical cancer research : CR · 2016Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatitis C Virus (HCV) infection is associated with chronically evolving disease and development of hepatocellular carcinoma (HCC), albeit the mechanism of HCC induction by HCV is still controversial. The nucleocapsid (core) protein of HCV has been shown to be directly implicated in cellular transformation and immortalization, enhancing the effect of oncogenes and decreasing the one of tumor suppressor genes, as RB1 and its protein product pRB. With the aim of identifying novel molecular mechanisms of hepatocyte transformation by HCV, we examined the effect of HCV core protein on the expression of the whole Retinoblastoma (RB) family of tumor and growth suppressor factors, i.e. pRb, p107 and pRb2/p130.
methodsWe used a model system consisting of the HuH-7, HCV-free, human hepatocellular carcinoma cell line and of the HuH-7-CORE cells derived from the former and constitutively expressing the HCV core protein. We determined pRb, p107 and pRb2/p130 protein and mRNA amount of the respective genes RB1, RBL1 and RBL2, RBL2 promoter activity and methylation as well as DNA methyltransferase 1 (DNMT1) and 3b (DNMT3b) expression level. The effect of pRb2/p130 over-expression on the HCV core-expressing HuH-7-CORE cells was also evaluated.
resultsWe found that the HCV core protein expression down-regulated pRb2/p130 protein and mRNA levels in HuH-7-CORE cells by inducing promoter hyper-methylation with the concomitant up-regulation of DNMT1 and DNMT3b expression. When pRb2/p130 expression was artificially re-established in HuH-7-CORE cells, cell cycle analysis outlined an accumulation in the G0/G1 phase, as expected.
conclusionsHCV core appears indeed able to significantly down-regulate the expression and the function of two out of three RB family tumor and growth suppressor factors, i.e. pRb and pRb2/p130. The functional consequences at the level of cell cycle regulation, and possibly of more complex cell homeostatic processes, may represent a plausible molecular mechanism involved in liver transformation by HCV.
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