ArticleMolecular cancer2014
Hepatitis B virus X protein accelerates hepatocarcinogenesis with partner survivin through modulating miR-520b and HBXIP.
Article in Molecular cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 59 citations in OpenAlex.
- The Beneficial Effects of Resveratrol on Hepatocellular Carcinoma and Nonalcoholic Fatty Liver Disease: Modulation of Apoptosis, Autophagy, Inflammation, and Oxidative Stress.Food science & nutrition · 2025Review
- Research progress on oncoprotein hepatitis B X‑interacting protein (Review).Molecular medicine reports · 2024Review
- Dysregulated microRNAs as a biomarker for diagnosis and prognosis of hepatitis B virus-associated hepatocellular carcinoma.World journal of gastroenterology · 2023Review
- Role of hepatitis B virus non-structural protein HBx on HBV replication, interferon signaling, and hepatocarcinogenesis.Frontiers in microbiology · 2023Review
- Mechanism of HBx carcinogenesis interaction with non-coding RNA in hepatocellular carcinoma.Frontiers in oncology · 2023Review
- Review
- FGF16 regulated by miR-520b enhances the cell proliferation of lung cancer.Open medicine (Warsaw, Poland) · 2021Article
- Hypermethylation of GNA14 and its tumor-suppressive role in hepatitis B virus-related hepatocellular carcinoma.Theranostics · 2021Article
- Development of an Autophagy-Based and Stemness-Correlated Prognostic Model for Hepatocellular Carcinoma Using Bulk and Single-Cell RNA-Sequencing.Frontiers in cell and developmental biology · 2021Article
- The Functions of Hepatitis B Virus Encoding Proteins: Viral Persistence and Liver Pathogenesis.Frontiers in immunology · 2021Review
- Autophagy-Related Gene Pairs Signature for the Prognosis of Hepatocellular Carcinoma.Frontiers in molecular biosciences · 2021Article
- Review
- The Potential Therapeutic Role of Exosomal MicroRNA-520b Derived from Normal Fibroblasts in Pancreatic Cancer.Molecular therapy. Nucleic acids · 2020Article
- The effects of HBXIP on the biological functions of tongue squamous cell carcinoma cells and correlation with PI3K/Akt.Translational cancer research · 2020Article
- Survivin expression starts before hepatocellular cancer development in the liver of chronic hepatitis B patients: a pilot, cross-sectional study.Przeglad gastroenterologiczny · 2020Article
- MLK3 is a newly identified microRNA-520b target that regulates liver cancer cell migration.PloS one · 2020Article
- Review
- MiR-520b restrains cell growth by targeting HDAC4 in lung cancer.Thoracic cancer · 2018Article
- An autophagy-related gene expression signature for survival prediction in multiple cohorts of hepatocellular carcinoma patients.Oncotarget · 2018Article
- Inhibitory effects of resveratrol on hepatitis B virus X protein-induced hepatocellular carcinoma.Journal of veterinary science · 2017Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatitis B virus X protein (HBx) plays crucial roles in hepatocarcinogenesis. However, the underlying mechanism remains elusive. We have reported that HBx is able to up-regulate survivin in hepatocellular carcinoma tissues. The oncopreotein hepatitis B X-interacting protein (HBXIP), a target of miR-520b, is involved in the development of cancer. In this study, we focus on the investigation of hepatocarcinogenesis mediated by HBx.
methodsThe expression of HBx and survivin was examined in the liver tissues of HBx-Tg mice. The effect of HBx/survivin on the growth of LO2-X-S cells was determined by colony formation and transplantation in nude mice. The effect of HBx/survivin on promoter of miR-520b was determined by Western blot analysis, luciferase reporter gene assay, co-immunoprecipitation (co-IP) and chromatin immunoprecipitation (ChIP), respectively. The expression of HBx, survivin and HBXIP was detected by immunohistochemistry and real-time PCR in clinical HCC tissues, respectively. The DNA demethylation of HBXIP promoter was examined. The functional influence of miR-520b and HBXIP on proliferation of hepatoma cells was analyzed by MTT, colony formation, EdU and transplantation in nude mice in vitro and in vivo.
resultsIn this study, we provided evidence that HBx up-regulated survivin in the liver cancer tissues of HBx-Tg mice aged 18 M. The engineered LO2 cell lines with survivin and/or HBx were successfully established, termed LO2-X-S. MiR-520b was down-regulated in LO2-X-S cells and clinical HCC tissues. Our data revealed that HBx survivin-dependently down-regulated miR-520b through interacting with Sp1 in the cells. HBXIP was highly expressed in LO2-X-S cells, liver cancer tissues of HBx-Tg mice aged 18 M and clinical HCC tissues (75.17%, 112/149). The expression level of HBXIP was positively associated with those of HBx or survivin in clinical HCC tissues. In addition, we showed that HBx survivin-dependently up-regulated HBXIP through inducing demethylation of HBXIP promoter in LO2-X-S cells and clinical HCC tissues. In function, low level miR-520b and high level HBXIP mediated by HBx with partner survivin contributed to the growth of LO2-X-S cells in vitro and in vivo.
conclusionHBx accelerates hepatocarcinogenesis with partner survivin through modulating tumor suppressor miR-520b and oncoprotein HBXIP.
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