ArticleClinical cancer research : an official journal of the American Association for Cancer Research2010
Hepatitis C virus proteins modulate microRNA expression and chemosensitivity in malignant hepatocytes.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Modulation of pancreatic cancer cell sensitivity to FOLFIRINOX through microRNA-mediated regulation of DNA damage.Nature communications · 2021Pooled it
- Trial
- Targeting CXCR6 Disrupts β-Catenin Signaling and Enhances Sorafenib Response in Hepatocellular Carcinoma.Cancers · 2025Article
- Resistance of first-line targeted drugs in hepatocellular carcinoma: the epigenetic regulation mechanisms.Cell death & disease · 2025Review
- Identification of exosomal microRNAs and related hub genes associated with imatinib resistance in chronic myeloid leukemia.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Hepatocellular Carcinoma Prevention in the Era of Hepatitis C Elimination.International journal of molecular sciences · 2023Review
- Systemic therapies in hepatocellular carcinoma: Existing and emerging biomarkers for treatment response.Frontiers in oncology · 2022Review
- Review
- Cell death pathways and viruses: Role of microRNAs.Molecular therapy. Nucleic acids · 2021Review
- MicroRNAs as Predictive Biomarkers of Resistance to Targeted Therapies in Gastrointestinal Tumors.Biomedicines · 2021Review
- Sorafenib in the Treatment of Virus-Related HCC: Differences Between HCV and HBV.OncoTargets and therapy · 2021Article
- Circulating microRNAs associated with liver fibrosis in chronic hepatitis C patients.Biochemistry and biophysics reports · 2020Article
- Modulation of Biliary Cancer Chemo-Resistance Through MicroRNA-Mediated Rewiring of the Expansion of CD133+ Cells.Hepatology (Baltimore, Md.) · 2020Article
- A novel microRNA boosts hyper-β-oxidation of fatty acids in liver by impeding CEP350-mediated sequestration of PPARα and thus restricts chronic hepatitis C.RNA biology · 2020Article
- Observational
- The emerging role of microRNAs and long noncoding RNAs in drug resistance of hepatocellular carcinoma.Molecular cancer · 2019Review
- Molecular Mechanisms Driving Progression of Liver Cirrhosis towards Hepatocellular Carcinoma in Chronic Hepatitis B and C Infections: A Review.International journal of molecular sciences · 2019Review
- Non-coding RNAs: Emerging Regulators of Sorafenib Resistance in Hepatocellular Carcinoma.Frontiers in oncology · 2019Review
- MicroRNA-221 inhibits human papillomavirus 16 E1-E2 mediated DNA replication through activating SOCS1/Type I IFN signaling pathway.International journal of clinical and experimental pathology · 2019Article
- Clinical significances and diagnostic utilities of both miR-215 and squamous cell carcinoma antigen-IgM versus alpha-fetoprotein in Egyptian patients with hepatitis C virus-induced hepatocellular carcinoma.Clinical and experimental gastroenterology · 2019Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeHepatocellular cancer (HCC) is highly resistant to chemotherapy and is associated with poor prognosis. Chronic hepatitis C virus (HCV) infection is a major cause of HCC. However, the effect of viral proteins in mediating chemosensitivity in tumor cells is unknown. We postulated that HCV viral proteins could modulate therapeutic responses by altering host cell microRNA (miRNA) expression. EXPERIMENTAL
designHepG2 malignant hepatocytes were stably transfected with full-length HCV genome (Hep-394) or an empty vector (Hep-SWX). MiRNA profiling was done by using a custom microarray, and the expression of selected miRNAs was validated by real-time PCR. Protein expression was assessed by Western blotting, whereas caspase activation was assessed by a luminometric assay.
resultsThe IC(50) to sorafenib was lower in Hep-394 compared with Hep-SWX control cells. Alterations in miRNA expression occurred with 10 miRNAs downregulated >2-fold and 23 miRNAs upregulated >2-fold in Hep-394 cells compared with controls. Of these, miR-193b was overexpressed by 5-fold in Hep-394 cells. miR-193b was predicted to target Mcl-1, an antiapoptotic protein that can modulate the response to sorafenib. The expression of Mcl-1 was decreased, and basal caspase-3/7 activity and poly ADP ribose polymerase cleavage were increased in Hep-394 cells compared with controls. Moreover, transfection with precursors to miR-193b decreased both Mcl-1 expression and the IC(50) to sorafenib.
conclusionsCellular expression of full-length HCV increases sensitivity to sorafenib by the miRNA-dependent modulation of Mcl-1 and apoptosis. Modulation of miRNA responses may be a useful strategy to enhance response to chemotherapy in HCC.
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