ArticleGut2020
Hepatitis B protein HBx binds the DLEU2 lncRNA to sustain cccDNA and host cancer-related gene transcription.
Article in Gut, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 139 citations in OpenAlex.
- The long noncoding RNA MAPKAPK5-AS1 promotes the formation of hepatitis B virus cccDNA by modulating the expression of NABP1.Virulence · 2026Article
- Natural products targeting hepatitis B virus X protein and HBx-associated pathways in HBV-related hepatocellular carcinoma: mechanisms and therapeutic potential.Pharmaceutical biology · 2026Review
- Current progress and role of lncRNAs in HBV infection and progression of hepatocellular carcinoma.Genes & diseases · 2026Review
- Viral persistence and host-state remodeling in virus-associated cancers.Archives of microbiology · 2026Review
- Targeting ferroptosis induction via nanomaterials in hepatocellular carcinoma: an insight into mechanism and therapeutic potential.Journal of nanobiotechnology · 2026Review
- Validity of a seven-gene signature as a non-invasive biomarker for cirrhosis: a cross-sectional study in Egyptian patients with HBV infection.BMC gastroenterology · 2026Article
- The Janus face of host LncRNA in viral infections: Defender or collaborator?Communications biology · 2026Review
- Hepatitis B virus-induced hepatocellular carcinoma: HBx-associated epigenetic mechanisms and therapeutic opportunities.Cancer gene therapy · 2026Review
- Histone Methylation: A Pivotal Epigenetic Driver of the Malignant Transformation of MASLD-HCC.Journal of hepatocellular carcinoma · 2026Review
- Hepatitis B virus integration and hepatocarcinogenesis.Liver research (Beijing, China) · 2025Review
- Epitranscriptomic Regulation of Hepatitis B Virus by RNA 5-Methylcytosine: Functions, Mechanisms, and Therapeutic Potential.Viruses · 2025Review
- Epigenetic drugs against human DNA viruses and retroviruses.Antiviral research · 2025Review
- HBx mutant-regulated RPL13AP25 mediates suboptimal virological response to entecavir and HCC progression.Cancer cell international · 2025Article
- Perspectives on NcRNAs in HBV/cccDNA-driven HCC progression.Cancer cell international · 2025Review
- HBV-driven host chromatin accessibility changes affect liver metabolic pathways, iron homeostasis and promote a preneoplastic phenotype.Journal of experimental & clinical cancer research : CR · 2025Article
- [Occurrence risk of extrahepatic liver tumor with hepatitis B virus infection].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- Long Non-coding RNA FOXD2-AS1 Silencing Inhibits Malignant Behaviors of Ovarian Cancer Cells Via miR-324-3p/SOX4 Signaling Axis.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Influence of Occult Hepatitis B Infection on Blood Transfusion Safety and Its Countermeasures.Pathogens (Basel, Switzerland) · 2025Review
- Engineering artificial non-coding RNAs for targeted protein degradation.Nature chemical biology · 2025Article
- The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions.MedComm · 2025Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe HBV HBx regulatory protein is required for transcription from the covalently closed circular DNA (cccDNA) minichromosome and affects the epigenetic control of both viral and host cellular chromatin.
designWe explored, in relevant cellular models of HBV replication, the functional consequences of HBx interaction with DLEU2, a long non-coding RNA (lncRNA) expressed in the liver and increased in human hepatocellular carcinoma (HCC), in the regulation of host target genes and the HBV cccDNA.
resultsWe show that HBx binds the promoter region, enhances the transcription and induces the accumulation of DLEU2 in infected hepatocytes. We found that nuclear DLEU2 directly binds HBx and the histone methyltransferase enhancer of zeste homolog 2 (EZH2), the catalytic active subunit of the polycomb repressor complex 2 (PRC2) complex. Computational modelling and biochemical evidence suggest that HBx and EZH2 share two preferential binding sites in DLEU2 intron 1. HBx and DLEU2 co-recruitment on the cccDNA displaces EZH2 from the viral chromatin to boost transcription and viral replication. DLEU2-HBx association with target host promoters relieves EZH2 repression and leads to the transcriptional activation of a subset of EZH2/PRC2 target genes in HBV-infected cells and HBV-related HCCs.
conclusionsOur results highlight the ability of HBx to bind RNA to impact on the epigenetic control of both viral cccDNA and host genes and provide a new key to understand the role of DLEU2 and EZH2 overexpression in HBV-related HCCs and HBx contribution to hepatocytes transformation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.