ArticleGut2018
miR-135a-5p-mediated downregulation of protein tyrosine phosphatase receptor delta is a candidate driver of HCV-associated hepatocarcinogenesis.
Article in Gut, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Silencing of OIP5-AS1 Protects Endothelial Cells From ox-LDL-Triggered Injury by Regulating KLF5 Expression via Sponging miR-135a-5p.Frontiers in cardiovascular medicine · 2021Pooled it
- Identification of potential oncogenic miRNA clusters with a special focus on miR-106b/25 cluster-regulated networks and their clinical utility in hepatocellular carcinoma.Discover oncology · 2025Article
- The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions.MedComm · 2025Review
- Exploration of prognostic and treatment markers in hepatocellular carcinoma via GPCR-related genes analysis.Heliyon · 2024Article
- Placenta-derived exosomal miR-135a-5p promotes gestational diabetes mellitus pathogenesis by activating PI3K/AKT signalling pathway via SIRT1.Journal of cellular and molecular medicine · 2023Article
- Recent Updates on Viral Oncogenesis: Available Preventive and Therapeutic Entities.Molecular pharmaceutics · 2023Review
- Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance.Cellular & molecular biology letters · 2023Review
- Epigenetic and genetic inactivation of tumor suppressor miR-135a in non-small-cell lung cancer.Thoracic cancer · 2023Article
- CD24-associated ceRNA network reveals prognostic biomarkers in breast carcinoma.Scientific reports · 2023Article
- Co-Infection and Cancer: Host-Pathogen Interaction between Dendritic Cells and HIV-1, HTLV-1, and Other Oncogenic Viruses.Viruses · 2022Review
- Review
- Serum long non-coding RNA SCARNA10 serves as a potential diagnostic biomarker for hepatocellular carcinoma.BMC cancer · 2022Article
- Signaling Induced by Chronic Viral Hepatitis: Dependence and Consequences.International journal of molecular sciences · 2022Review
- Molecular pathogenesis: Connections between viral hepatitis-induced and non-alcoholic steatohepatitis-induced hepatocellular carcinoma.Frontiers in immunology · 2022Review
- Regulation of Gamma-Aminobutyric Acid Transaminase Expression and Its Clinical Significance in Hepatocellular Carcinoma.Frontiers in oncology · 2022Article
- GOLT1B Activation in Hepatitis C Virus-Infected Hepatocytes Links ER Trafficking and Viral Replication.Pathogens (Basel, Switzerland) · 2021Article
- Hepatitis B core antigen modulates exosomal miR-135a to target vesicle-associated membrane protein 2 promoting chemoresistance in hepatocellular carcinoma.World journal of gastroenterology · 2021Article
- Integrated bioinformatics analysis revealed the regulation of angiogenesis by tumor cells in hepatocellular carcinoma.Bioscience reports · 2021Article
- Molecular pathways in viral hepatitis-associated liver carcinogenesis: An update.World journal of clinical cases · 2021Review
- Profibrotic Signaling and HCC Risk during Chronic Viral Hepatitis: Biomarker Development.Journal of clinical medicine · 2021Review
Corrections and comments
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Authors and funding
23 authors at 7 institutions in 4 countries.
Funding
Abstract
BACKGROUND AND
aimsHCV infection is a leading risk factor of hepatocellular carcinoma (HCC). However, even after viral clearance, HCC risk remains elevated. HCV perturbs host cell signalling to maintain infection, and derailed signalling circuitry is a key driver of carcinogenesis. Since protein phosphatases are regulators of signalling events, we aimed to identify phosphatases that respond to HCV infection with relevance for hepatocarcinogenesis.
methodsWe assessed mRNA and microRNA (miRNA) expression profiles in primary human hepatocytes, liver biopsies and resections of patients with HCC, and analysed microarray and RNA-seq data from paired liver biopsies of patients with HCC. We revealed changes in transcriptional networks through gene set enrichment analysis and correlated phosphatase expression levels to patient survival and tumour recurrence.
resultsWe demonstrate that tumour suppressor protein tyrosine phosphatase receptor delta (PTPRD) is impaired by HCV infection in vivo and in HCC lesions of paired liver biopsies independent from tissue inflammation or fibrosis. In liver tissue adjacent to tumour, high PTPRD levels are associated with a dampened transcriptional activity of STAT3, an increase of patient survival from HCC and reduced tumour recurrence after surgical resection. We identified miR-135a-5p as a mechanistic regulator of hepatic PTPRD expression in patients with HCV.
conclusionsWe previously demonstrated that STAT3 is required for HCV infection. We conclude that HCV promotes a STAT3 transcriptional programme in the liver of patients by suppressing its regulator PTPRD via upregulation of miR-135a-5p. Our results show the existence of a perturbed PTPRD-STAT3 axis potentially driving malignant progression of HCV-associated liver disease.
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