ArticleArchives of toxicology2018
Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans.
Article in Archives of toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 64 citations in OpenAlex.
- Multi-omics data-based modeling reveals tumorigenesis- and prognosis-associated genes with clinical potential in lung adenocarcinoma.BMC cancer · 2025Article
- In vitro liver models for toxicological research.Drug metabolism and pharmacokinetics · 2025Review
- Identification of key genes and diagnostic model associated with circadian rhythms and Parkinson's disease by bioinformatics analysis.Frontiers in aging neuroscience · 2024Article
- miRNA-ome plasma analysis unveils changes in blood-brain barrier integrity associated with acute liver failure in rats.Fluids and barriers of the CNS · 2023Article
- Integration of bioinformatics analysis and experimental validation identifies plasma exosomal miR-103b/877-5p/29c-5p as diagnostic biomarkers for early lung adenocarcinoma.Cancer medicine · 2022Article
- Epigenetics in drug disposition & drug therapy: symposium report of the 24Drug metabolism reviews · 2022Review
- A risk score system based on a six-microRNA signature predicts the overall survival of patients with ovarian cancer.Journal of ovarian research · 2022Article
- Identification of key genes and pathways between mild-moderate and severe asthmatics via bioinformatics analysis.Scientific reports · 2022Article
- Genome-wide microRNA profiles identify miR-107 as a top miRNA associating with expression of the CYP3As and other drug metabolizing cytochrome P450 enzymes in the liver.Frontiers in pharmacology · 2022Article
- Insight into microRNAs-Mediated Communication between Liver and Brain: A Possible Approach for Understanding Acute Liver Failure?International journal of molecular sciences · 2021Review
- Role of Noncoding RNAs in Acetaminophen-Induced Liver Injury.Gene expression · 2021Review
- Identification of Translational microRNA Biomarker Candidates for Ketoconazole-Induced Liver Injury Using Next-Generation Sequencing.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Transcriptional and post-transcriptional regulation of the pregnane X receptor: a rationale for interindividual variability in drug metabolism.Archives of toxicology · 2021Review
- miR-15a-3p Protects Against Isoniazid-Induced Liver InjuryFrontiers in molecular biosciences · 2021Article
- LncRNA KCNQ1OT1 ameliorates the liver injury induced by acetaminophen through the regulation of miR-122-5p/CES2 axis.Molecular and cellular biochemistry · 2020Article
- circ-CBFB upregulates p66Shc to perturb mitochondrial dynamics in APAP-induced liver injury.Cell death & disease · 2020Article
- Long noncoding RNA LINC00844-mediated molecular network regulates expression of drug metabolizing enzymes and nuclear receptors in human liver cells.Archives of toxicology · 2020Article
- Knockdown of Long Noncoding RNAs Hepatocyte Nuclear Factor 1Molecular pharmacology · 2020Article
- Coordinated Regulation of UGT2B15 Expression by Long Noncoding RNA LINC00574 and hsa-miR-129-5p in HepaRG Cells.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Circulating microRNA Profiles in Acetaminophen Toxicity.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2020Observational
Corrections and comments
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Authors and funding
32 authors at 6 institutions in 2 countries.
Funding
Abstract
Acetaminophen (APAP) overdose is the leading cause of acute liver failure. Yet the mechanisms underlying adaptive tolerance toward APAP-induced liver injury are not fully understood. To better understand molecular mechanisms contributing to adaptive tolerance to APAP is an underpinning foundation for APAP-related precision medicine. In the current study, the mRNA and microRNA (miRNA) expression profiles derived from next generation sequencing data for APAP-treated (5 and 10 mM) HepaRG cells and controls were analyzed systematically. Putative miRNAs targeting key dysregulated genes involved in APAP hepatotoxicity were selected using in silico prediction algorithms, un-biased gene ontology, and network analyses. Luciferase reporter assays, RNA electrophoresis mobility shift assays, and miRNA pull-down assays were performed to investigate the role of miRNAs affecting the expression of dysregulated genes. Levels of selected miRNAs were measured in serum samples obtained from children with APAP overdose (58.6-559.4 mg/kg) and from healthy controls. As results, 2758 differentially expressed genes and 47 miRNAs were identified. Four of these miRNAs (hsa-miR-224-5p, hsa-miR-320a, hsa-miR-449a, and hsa-miR-877-5p) suppressed drug metabolizing enzyme (DME) levels involved in APAP-induced liver injury by downregulating HNF1A, HNF4A and NR1I2 expression. Exogenous transfection of these miRNAs into HepaRG cells effectively rescued them from APAP toxicity, as indicated by decreased alanine aminotransferase levels. Importantly, hsa-miR-320a and hsa-miR-877-5p levels were significantly elevated in serum samples obtained from children with APAP overdose compared to health controls. Collectively, these data indicate that hsa-miR-224-5p, hsa-miR-320a, hsa-miR-449a, and hsa-miR-877-5p suppress DME expression involved in APAP-induced hepatotoxicity and they contribute to an adaptive response in hepatocytes.
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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.