ArticlePloS one2011
Carboxyl-terminal truncated HBx regulates a distinct microRNA transcription program in hepatocellular carcinoma development.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Applications of next-generation sequencing analysis for the detection of hepatocellular carcinoma-associated hepatitis B virus mutations.Journal of biomedical science · 2018Pooled it
- Hepatitis B virus integration and hepatocarcinogenesis.Liver research (Beijing, China) · 2025Review
- HBV DNA integration gene CCDC91 is oncogenic and a potential therapeutic target for hepatocellular carcinoma.Communications biology · 2025Article
- Dysregulated microRNAs as a biomarker for diagnosis and prognosis of hepatitis B virus-associated hepatocellular carcinoma.World journal of gastroenterology · 2023Review
- Hepatitis B virus X protein mediated epigenetic alterations in the pathogenesis of hepatocellular carcinoma.Hepatology international · 2022Review
- MicroRNA let-7 and viral infections: focus on mechanisms of action.Cellular & molecular biology letters · 2022Review
- Inhibition of Protease Activated Receptor 2 Attenuates HBx-Induced Inflammation and Mitochondria Oxidative Stress.Infection and drug resistance · 2022Article
- Molecular pathways in viral hepatitis-associated liver carcinogenesis: An update.World journal of clinical cases · 2021Review
- LINC01348 suppresses hepatocellular carcinoma metastasis through inhibition of SF3B3-mediated EZH2 pre-mRNA splicing.Oncogene · 2021Article
- Cell death pathways and viruses: Role of microRNAs.Molecular therapy. Nucleic acids · 2021Review
- Emerging Regulatory Mechanisms Involved in Liver Cancer Stem Cell Properties in Hepatocellular Carcinoma.Frontiers in cell and developmental biology · 2021Review
- AnFrontiers in genetics · 2021Article
- Review
- Synergistic Effect of MC-LR and C-Terminal Truncated HBx on HepG2 Cells and Their Effects on PP2A Mediated Downstream Target of MAPK Signaling Pathway.Frontiers in genetics · 2020Article
- APLN promotes hepatocellular carcinoma through activating PI3K/Akt pathway and is a druggable target.Theranostics · 2019Article
- Micro-RNAs in hepatitis B virus-related chronic liver diseases and hepatocellular carcinoma.World journal of hepatology · 2018Review
- Hepatitis B virus X protein inhibits apoptosis by modulating endoplasmic reticulum stress response.Oncotarget · 2017Article
- HBeAg-induced miR-106b promotes cell growth by targeting the retinoblastoma gene.Scientific reports · 2017Article
- C-terminal truncated hepatitis B virus X protein regulates tumorigenicity, self-renewal and drug resistance via STAT3/Nanog signaling pathway.Oncotarget · 2017Article
- Mutations in Hepatitis-B X-Gene Region: Chronic Hepatitis-B versus Cirrhosis.Journal of clinical and diagnostic research : JCDR · 2017Article
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe biological pathways and functional properties by which misexpressed microRNAs (miRNAs) contribute to liver carcinogenesis have been intensively investigated. However, little is known about the upstream mechanisms that deregulate miRNA expressions in this process. In hepatocellular carcinoma (HCC), hepatitis B virus (HBV) X protein (HBx), a transcriptional trans-activator, is frequently expressed in truncated form without carboxyl-terminus but its role in miRNA expression and HCC development is unclear.
methodsHuman non-tumorigenic hepatocytes were infected with lentivirus-expressing full-length and carboxyl-terminal truncated HBx (Ct-HBx) for cell growth assay and miRNA profiling. Chromatin immunoprecipitation microarray was performed to identify the miRNA promoters directly associated with HBx. Direct transcriptional control was verified by luciferase reporter assay. The differential miRNA expressions were further validated in a cohort of HBV-associated HCC tissues using real-time PCR.
resultsHepatocytes expressing Ct-HBx grew significantly faster than the full-length HBx counterparts. Ct-HBx decreased while full-length HBx increased the expression of a set of miRNAs with growth-suppressive functions. Interestingly, Ct-HBx bound to and inhibited the transcriptional activity of some of these miRNA promoters. Notably, some of the examined repressed-miRNAs (miR-26a, -29c, -146a and -190) were also significantly down-regulated in a subset of HCC tissues with carboxyl-terminal HBx truncation compared to their matching non-tumor tissues, highlighting the clinical relevance of our data.
conclusionOur results suggest that Ct-HBx directly regulates miRNA transcription and in turn promotes hepatocellular proliferation, thus revealing a viral contribution of miRNA deregulation during hepatocarcinogenesis.
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