ArticleHepatology communications2017
Interferon-alpha-induced hepatitis C virus clearance restores p53 tumor suppressor more than direct-acting antivirals.
Article in Hepatology communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 23 citations in OpenAlex.
- Review
- Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy.Biomedicines · 2023Review
- Long noncoding RNA CERS6-AS1 modulates glucose metabolism and tumor progression in hepatocellular carcinoma by promoting the MDM2/p53 signaling pathway.Cell death discovery · 2022Article
- Hepatitis C Virus-Induced ROS/JNK Signaling Pathway Activates the E3 Ubiquitin Ligase Itch to Promote the Release of HCV Particles via Polyubiquitylation of VPS4A.Journal of virology · 2022Article
- Integrated stress response in hepatitis C promotes Nrf2-related chaperone-mediated autophagy: A novel mechanism for host-microbe survival and HCC development in liver cirrhosis.Seminars in cell & developmental biology · 2020Review
- Hepatocellular Carcinoma Mechanisms Associated with Chronic HCV Infection and the Impact of Direct-Acting Antiviral Treatment.Journal of hepatocellular carcinoma · 2020Review
- Mutant p53 as a Regulator and Target of Autophagy.Frontiers in oncology · 2020Review
- Regulation of Autophagy in Cells Infected With Oncogenic Human Viruses and Its Impact on Cancer Development.Frontiers in cell and developmental biology · 2020Review
- Review
- Article
- Screening for Antiviral Medaka Haploid Embryonic Stem Cells by Genome Wide Mutagenesis.Marine biotechnology (New York, N.Y.) · 2019Article
- Immunological Dynamics Associated with Direct-Acting Antiviral Therapies in Naive and Experimented HCV Chronic-Infected Patients.Mediators of inflammation · 2019Article
- Chaperone-Mediated Autophagy Promotes Beclin1 Degradation in Persistently Infected Hepatitis C Virus Cell Culture.The American journal of pathology · 2018Article
- Review
- Targeting Chaperone-Mediated Autophagy for Disease Therapy.Current pharmacology reports · 2018Article
- Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine.Journal of hepatology · 2018Review
- Activation of PERK-Nrf2 oncogenic signaling promotes Mdm2-mediated Rb degradation in persistently infected HCV culture.Scientific reports · 2017Article
- Chaperone-mediated autophagy compensates for impaired macroautophagy in the cirrhotic liver to promote hepatocellular carcinoma.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanism why hepatitis C virus (HCV) clearance by direct-acting antivirals (DAAs) does not eliminate the risk of hepatocellular carcinoma (HCC) among patients with advanced cirrhosis is unclear. Many viral and bacterial infections degrade p53 in favor of cell survival to adapt an endoplasmic reticulum (ER)-stress response. In this study, we examined whether HCV clearance by interferon-alpha or DAAs normalizes the ER stress and restores the expression of p53 tumor suppressor in cell culture. We found that HCV infection induces chronic ER stress and unfolded protein response in untransformed primary human hepatocytes. The unfolded protein response induces chaperone-mediated autophagy (CMA) in infected primary human hepatocytes and Huh-7.5 cells that results in degradation of p53 and induced expression of mouse double minute 2 (Mdm2). Inhibition of p53/Mdm2 interactions by small molecule (nutlin-3) or silencing Mdm2 did not rescue the p53 degradation, indicating that HCV infection induces degradation of p53 independent of the Mdm2 pathway. Interestingly, we found that HCV infection degrades p53 in a lysosome-dependent mechanism because lysosome-associated membrane protein 2A silencing restored p53 degradation. Our results show that HCV clearance induced by interferon-alpha-based antiviral therapies normalizes the ER-stress response and restores p53, whereas HCV clearance by DAAs does neither. We show that decreased expression of p53 in HCV-infected cirrhotic liver is associated with expression of chaperones associated with ER stress and the CMA response.
Identifiers
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.