ArticleCell death & disease2021
Anti-miR-518d-5p overcomes liver tumor cell death resistance through mitochondrial activity.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Mitochondria-Targeting microRNAs (mitomiRs): Potential Mediators of Environmental Mitoepigenetics in Mammalian Spermatogenesis.Biomolecules · 2026Review
- PRICE: direct and robust detection of microRNAs at single-nucleotide resolution.Nature communications · 2026Article
- Identification of Circulating MiR-4651 as Novel Biomarker for Metabolic Dysfunction-Associated Steatotic Liver Disease.Gastro hep advances · 2026Article
- Resistance of first-line targeted drugs in hepatocellular carcinoma: the epigenetic regulation mechanisms.Cell death & disease · 2025Review
- Cell-free and extracellular vesicle microRNAs with clinical utility for solid tumors.Molecular oncology · 2025Review
- The epigenetic basis of hepatocellular carcinoma - mechanisms and potential directions for biomarkers and therapeutics.British journal of cancer · 2025Review
- Targeting ncRNAs to overcome metabolic reprogramming‑mediated drug resistance in cancer (Review).International journal of oncology · 2025Review
- Mitochondrial microRNAs (mitomiRs) as emerging biomarkers and therapeutic targets for chronic human diseases.Frontiers in genetics · 2025Review
- Combatting cellular immortality in cancers by targeting the shelterin protein complex.Biology direct · 2024Article
- Biomarkers for diagnosis and therapeutic options in hepatocellular carcinoma.Molecular cancer · 2024Review
- Programmed cell death in hepatocellular carcinoma: mechanisms and therapeutic prospects.Cell death discovery · 2024Review
- Metallothionein-3 is a multifunctional driver that modulates the development of sorafenib-resistant phenotype in hepatocellular carcinoma cells.Biomarker research · 2024Article
- Review
- Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy.Biomedicines · 2023Review
- Research progress of circulating non-coding RNA in diagnosis and treatment of hepatocellular carcinoma.Frontiers in oncology · 2023Review
- Little things with significant impact: miRNAs in hepatocellular carcinoma.Frontiers in oncology · 2023Review
- Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective.Signal transduction and targeted therapy · 2022Review
- Article
- The spike of SARS-CoV-2 promotes metabolic rewiring in hepatocytes.Communications biology · 2022Article
- Mitochondrial Dysfunction and Chronic Liver Disease.Current issues in molecular biology · 2022Review
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Authors and funding
31 authors at 10 institutions in 5 countries.
Funding
Abstract
Dysregulation of miRNAs is a hallmark of cancer, modulating oncogenes, tumor suppressors, and drug responsiveness. The multi-kinase inhibitor sorafenib is one of the first-line drugs for advanced hepatocellular carcinoma (HCC), although the outcome for treated patients is heterogeneous. The identification of predictive biomarkers and targets of sorafenib efficacy are sorely needed. Thus, selected top upregulated miRNAs from the C19MC cluster were analyzed in different hepatoma cell lines compared to immortalized liver human cells, THLE-2 as control. MiR-518d-5p showed the most consistent upregulation among them. Thus, miR-518d-5p was measured in liver tumor/non-tumor samples of two distinct cohorts of HCC patients (n = 16 and n = 20, respectively). Circulating miR-518d-5p was measured in an independent cohort of HCC patients receiving sorafenib treatment (n = 100), where miR-518d-5p was analyzed in relation to treatment duration and patient's overall survival. In vitro and in vivo studies were performed in human hepatoma BCLC3 and Huh7 cells to analyze the effect of miR-518d-5p inhibition/overexpression during the response to sorafenib. Compared with healthy individuals, miR-518d-5p levels were higher in hepatic and serum samples from HCC patients (n = 16) and in an additional cohort of tumor/non-tumor paired samples (n = 20). MiR-518d-5p, through the inhibition of c-Jun and its mitochondrial target PUMA, desensitized human hepatoma cells and mouse xenograft to sorafenib-induced apoptosis. Finally, serum miR-518d-5p was assessed in 100 patients with HCC of different etiologies and BCLC-stage treated with sorafenib. In BCLC-C patients, higher serum miR-518d-5p at diagnosis was associated with shorter sorafenib treatment duration and survival. Hence, hepatic miR-518d-5p modulates sorafenib resistance in HCC through inhibition of c-Jun/PUMA-induced apoptosis. Circulating miR-518d-5p emerges as a potential lack of response biomarker to sorafenib in BCLC-C HCC patients.
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