AI Article Synopsis
- The study investigates how hepatitis B virus (HBV) integration contributes to the risk of hepatocellular carcinoma (HCC) by analyzing HBV-positive HCC cell lines through transcriptome sequencing.
- Researchers identified a chimeric fusion transcript called HBx-LINE1 that has tumor-promoting effects and is present in about 23.3% of HBV-associated HCC tumors, linking it to poorer patient outcomes.
- The findings suggest that HBx-LINE1 enhances β-catenin activity and activates Wnt signaling, which may increase susceptibility to cancer and indicate a new target for understanding HCC mechanisms.
Article Abstract
The mutagenic effect of hepatitis B (HBV) integration in predisposing risk to hepatocellular carcinoma (HCC) remains elusive. In this study, we performed transcriptome sequencing of HBV-positive HCC cell lines and showed transcription of viral-human gene fusions from the site of genome integrations. We discovered tumor-promoting properties of a chimeric HBx-LINE1 that, intriguingly, functions as a hybrid RNA. HBx-LINE1 can be detected in 23.3% of HBV-associated HCC tumors and correlates with poorer patient survival. HBx-LINE1 transgenic mice showed heightened susceptibility to diethylnitrosamine-induced tumor formation. We further show that HBx-LINE1 expression affects β-catenin transactivity, which underlines a role in activating Wnt signaling. Thus, this study identifies a viral-human chimeric fusion transcript that functions like a long noncoding RNA to promote HCC.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ccr.2014.01.030 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
An enrichment protocol and analysis pipeline for long read sequencing of the hepatitis B virus transcriptome.
J Gen Virol
May 2023
Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Hepatitis B virus (HBV) is one of the smallest human DNA viruses and its 3.2 Kb genome encodes multiple overlapping open reading frames, making its viral transcriptome challenging to dissect. Previous studies have combined quantitative PCR and Next Generation Sequencing to identify viral transcripts and splice junctions, however the fragmentation and selective amplification used in short read sequencing precludes the resolution of full length RNAs.
View Article and Find Full Text PDFNatural Killer Cells and T Cells in Hepatocellular Carcinoma and Viral Hepatitis: Current Status and Perspectives for Future Immunotherapeutic Approaches.
Cells
May 2021
Roswell Park Comprehensive Cancer Center, Department of Immunology, Elm and Carlton Streets, Buffalo, NY 14263, USA.
Natural killer (NK) cells account for 25-50% of the total number of hepatic lymphocytes, which implicates that NK cells play an important role in liver immunity. The frequencies of both circulating and tumor infiltrating NK cells are positively correlated with survival benefit in hepatocellular cancer (HCC) and have prognostic implications, which suggests that functional impairment in NK cells and HCC progression are strongly associated. In HCC, T cell exhaustion is accompanied by the interaction between immune checkpoint ligands and their receptors on tumor cells and antigen presenting cells (APC).
View Article and Find Full Text PDFDeep sequencing of liver explant transcriptomes reveals extensive expression from integrated hepatitis B virus DNA.
J Viral Hepat
November 2020
Department of Infectious Diseases, Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). Integration of HBV DNA into the human genome may contribute to oncogenesis and to the production of the hepatitis B surface antigen (HBsAg). Whether integrations contribute to HBsAg levels in the blood is poorly known.
View Article and Find Full Text PDFIn silico designing of peptide based vaccine for Hepatitis viruses using reverse vaccinology approach.
Infect Genet Evol
October 2020
Department of Life Sciences, Presidency University, Kolkata, India. Electronic address:
Five different Hepatitis virus from different viral species cause viral-hepatitis, which is a life threatening disease leading to a high number of loss of lives every year. The mode of infection and transmission is different for each species and mostly spreads by direct contact and body fluids (for HBV and HCV). No such vaccine is available that can cure all types of Hepatitis with cross-protection.
View Article and Find Full Text PDFAxicabtagene ciloleucel CD19 CAR-T cell therapy results in high rates of systemic and neurologic remissions in ten patients with refractory large B cell lymphoma including two with HIV and viral hepatitis.
J Hematol Oncol
January 2020
Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, The Bronx, NY, USA.
Axicabtagene ciloleucel (Axi-cel) is a CD-19 Chimeric Antigen Receptor T cell therapy approved for the treatment of relapsed/refractory diffuse large B cell lymphoma. We treated ten patients with DLBCL post-FDA approval in an inner-city tertiary center in the Bronx. Eight patients (80%) had received ≥ 3 lines of therapy, six patients had received prior radiation, and seven had recurrent disease after prior autologous hematopoietic stem cell transplant (AHCT).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!