ArticleHepatology (Baltimore, Md.)2010
c-Jun mediates hepatitis C virus hepatocarcinogenesis through signal transducer and activator of transcription 3 and nitric oxide-dependent impairment of oxidative DNA repair.
Article in Hepatology (Baltimore, Md.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 54 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
54 citing papers in PubMed, 99 citations in OpenAlex.
- The spatiotemporal heterogeneity of reactive oxygen species in the malignant transformation of viral hepatitis to hepatocellular carcinoma: a new insight.Cellular & molecular biology letters · 2025Review
- Integrative analysis of serum proteomics and transcriptomics in hepatitis C.Virology journal · 2025Article
- Liver cancer development driven by the AP-1/c-Jun~Fra-2 dimer through c-Myc.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- STAT3 Decoy Oligodeoxynucleotides Suppress Liver Inflammation and Fibrosis in Liver Cancer Cells and a DDC-Induced Liver Injury Mouse Model.Molecules (Basel, Switzerland) · 2024Article
- LIN28 and histone H3K4 methylase induce TLR4 to generate tumor-initiating stem-like cells.iScience · 2023Article
- Gut-derived Endotoxin-TLR4 Signaling Drives MYC-Ig Translocation to Promote Lymphoproliferation through c-JUN and STAT3 Activation.Molecular cancer research : MCR · 2023Article
- The Role of JAK/STAT Pathway in Fibrotic Diseases: Molecular and Cellular Mechanisms.Biomolecules · 2023Review
- Article
- In-depth analysis of the expression and functions of signal transducers and activators of transcription in human ovarian cancer.Frontiers in oncology · 2022Article
- Role of hepatitis c virus in hepatocellular carcinoma and neurological disorders: an overview.Frontiers in oncology · 2022Review
- DoesCells · 2021Review
- JNK signaling as a target for anticancer therapy.Pharmacological reports : PR · 2021Review
- Fluorescent probe for the imaging of superoxide and peroxynitrite during drug-induced liver injury.Chemical science · 2021Article
- NAP1L1 Functions as a Tumor PromoterFrontiers in cell and developmental biology · 2021Article
- β-Cyclodextrin modified Pt(II) metallacycle-based supramolecular hyperbranched polymer assemblies for DOX delivery to liver cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- NO and hepatocellular cancer.British journal of pharmacology · 2020Review
- Schistosoma mansoni Egg-Secreted Antigens Activate Hepatocellular Carcinoma-Associated Transcription Factors c-Jun and STAT3 in Hamster and Human Hepatocytes.Hepatology (Baltimore, Md.) · 2020Article
- Comprehensive bioinformatics analysis of critical lncRNAs, mRNAs and miRNAs in non‑alcoholic fatty liver disease.Molecular medicine reports · 2019Article
- Liver carcinogenesis by FOS-dependent inflammation and cholesterol dysregulation.The Journal of experimental medicine · 2017Article
- Hepatitis C virus promotes hepatocellular carcinogenesis by targeting TIPE2, a new regulator of DNA damage response.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
Corrections and comments
- Erratum issued
- Retracted
Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
unlabelledHepatocellular carcinoma (HCC) occurs in a significant number of patients with hepatitis C virus (HCV) infection. HCV causes double-strand DNA breaks and enhances the mutation frequency of proto-oncogenes and tumor suppressors. However, the underlying mechanisms for these oncogenic events are still elusive. Here, we studied the role of c-Jun, signal transducer and activator of transcription 3 (STAT3), and nitric oxide (NO) in spontaneous and diethylnitrosamine (DEN)-initiated and/or phenobarbital (Pb)-promoted HCC development using HCV core transgenic (Tg) mice. The viral core protein induces hepatocarcinogenesis induction as a tumor initiator under promotion by Pb treatment alone. Conditional knockout of c-jun and stat3 in hepatocytes achieves a nearly complete, additive effect on prevention of core-induced spontaneous HCC or core-enhanced HCC incidence caused by DEN/Pb. Core protein induces hepatocyte proliferation and the expression of inflammatory cytokines (interleukin-6, tumor necrosis factor-alpha, interleukin-1) and inducible NO synthase (iNOS); the former is dependent on c-Jun and STAT3, and the latter on c-Jun. Oxidative DNA damage repair activity is impaired by the HCV core protein due to reduced DNA glycosylase activity for the excision of 8-oxo-2'-deoxyguanosine. This impairment is abrogated by iNOS inhibition or c-Jun deficiency, but aggravated by the NO donor or iNOS-inducing cytokines. The core protein also suppresses apoptosis mediated by Fas ligand because of c-Jun-dependent Fas down-regulation.
conclusionThese results indicate that the HCV core protein potentiates chemically induced HCC through c-Jun and STAT3 activation, which in turn, enhances cell proliferation, suppresses apoptosis, and impairs oxidative DNA damage repair, leading to hepatocellular transformation.
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What OpenQuestion holds
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.