Academic Journal
Hepatitis B protein HBx binds the DLEU2 lncRNA to sustain cccDNA and host cancer-related gene transcription
| العنوان: | Hepatitis B protein HBx binds the DLEU2 lncRNA to sustain cccDNA and host cancer-related gene transcription |
|---|---|
| المؤلفون: | Salerno, Debora, Chiodo, Letizia, Alfano, Vincenzo, Floriot, Oceane, Cottone, Grazia, Paturel, Alexia, Pallocca, Matteo, Plissonnier, Marie‐laure, Jeddari, Safaa, Belloni, Laura, Zeisel, Mirjam, B., Levrero, Massimo, Guerrieri, Francesca |
| المساهمون: | Italian Institute of Technology = Istituto Italiano di Tecnologia (IIT), Università Campus Bio-Medico di Roma / University Campus Bio-Medico of Rome (UCBM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard Lyon -Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Palermo - University of Palermo, National Cancer Institute Regina Elena Rome, Italy, Università degli Studi di Roma "La Sapienza" = Sapienza University Rome (UNIROMA) |
| المصدر: | ISSN: 0017-5749. |
| بيانات النشر: | CCSD BMJ Publishing Group |
| سنة النشر: | 2020 |
| المجموعة: | HAL Lyon 1 (University Claude Bernard Lyon 1) |
| مصطلحات موضوعية: | hepatitis B, hepatocellular carcinoma, liver, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology |
| الوصف: | International audience ; Objective The 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.Design We 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.Results We 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.Conclusions Our 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/32114505; PUBMED: 32114505; PUBMEDCENTRAL: PMC7569396 |
| DOI: | 10.1136/gutjnl-2019-319637 |
| الاتاحة: | https://hal.science/hal-03851058 https://hal.science/hal-03851058v1/document https://hal.science/hal-03851058v1/file/gutjnl-2019-319637.pdf https://doi.org/10.1136/gutjnl-2019-319637 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.390BE267 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1136/gutjnl-2019-319637 |
|---|