ArticleThe American journal of pathology2017
miRNA-122 Protects Mice and Human Hepatocytes from Acetaminophen Toxicity by Regulating Cytochrome P450 Family 1 Subfamily A Member 2 and Family 2 Subfamily E Member 1 Expression.
Article in The American journal of pathology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 49 citations in OpenAlex.
- Deciphering cytochrome P450 reductase role in MASLD: molecular mechanisms and pathophysiological implications.Nature reviews. Gastroenterology & hepatology · 2026Review
- Diploid hepatocytes resist acetaminophen-induced liver injury through suppressed JNK signaling.Cell death & disease · 2026Article
- miR-375 protects against acetaminophen-induced acute liver failure by orchestrating pharmacogene expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Aryl Hydrocarbon Receptor Establishes a Delicate Balance between the Level of the Trace Amine Tryptamine and Monoamine Oxidase Activity in the Brain and Periphery in Health and Conditions such as Neurodegenerative, Neurodevelopmental, and Psychiatric Disorders.Current neuropharmacology · 2025Review
- New insights into coordinated regulation of AHR promoter transcription; molecular mechanisms and therapeutic targets.International journal of biological sciences · 2025Review
- Potential of oligonucleotide- and protein/peptide-based therapeutics in the management of toxicant/stressor-induced diseases.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Prenatal cigarette smoke exposure sensitizes acetaminophen-induced liver injury by modulating miR-34a-5p in male offspring mice.Frontiers in cell and developmental biology · 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
- The complex biology of aryl hydrocarbon receptor activation in cancer and beyond.Biochemical pharmacology · 2023Review
- miR-122 dysregulation is associated with type 2 diabetes mellitus-induced dyslipidemia and hyperglycemia independently of its rs17669 variant.Molecular biology reports · 2023Article
- Roles of Non-Coding RNAs in Primary Biliary Cholangitis.Frontiers in molecular biosciences · 2022Review
- 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
- Hypoxia-inducible factor-1α-dependent induction of miR122 enhances hepatic ischemia tolerance.The Journal of clinical investigation · 2021Article
- N-Acetyl Cysteine Overdose Inducing Hepatic Steatosis and Systemic Inflammation in Both Propacetamol-Induced Hepatotoxic and Normal Mice.Antioxidants (Basel, Switzerland) · 2021Article
- Where the Aryl Hydrocarbon Receptor Meets the microRNAs: Literature Review of the Last 10 Years.Frontiers in molecular biosciences · 2021Review
- 2,3,5,4'-Tetrahydroxy-stilbene-2-Pharmaceutical biology · 2020Article
- Epigenetic Regulations of AhR in the Aspect of Immunomodulation.International journal of molecular sciences · 2020Review
- Role of B Cell Lymphoma 2 in the Regulation of Liver Fibrosis in miR-122 Knockout Mice.Biology · 2020Article
- Acetaminophen-Induced Liver Injury Alters Expression and Activities of Cytochrome P450 Enzymes in an Age-Dependent Manner in Mouse Liver.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Acetaminophen toxicity is a leading cause of acute liver failure (ALF). We found that miRNA-122 (miR-122) is down-regulated in liver biopsy specimens of patients with ALF and in acetaminophen-treated mice. A marked decrease in the primary miR-122 expression occurs in mice on acetaminophen overdose because of suppression of its key transactivators, hepatocyte nuclear factor (HNF)-4α and HNF6. More importantly, the mortality rates of male and female liver-specific miR-122 knockout (LKO) mice were significantly higher than control mice when injected i.p. with an acetaminophen dose not lethal to the control. LKO livers exhibited higher basal expression of cytochrome P450 family 2 subfamily E member 1 (CYP2E1) and cytochrome P450 family 1 subfamily A member 2 (CYP1A2) that convert acetaminophen to highly reactive N-acetyl-p-benzoquinone imine. Upregulation of Cyp1a2 primary transcript and mRNA in LKO mice correlated with the elevation of aryl hydrocarbon receptor (AHR) and mediator 1 (MED1), two transactivators of Cyp1a2. Analysis of ChIP-seq data in the ENCODE (Encyclopedia of DNA Element) database identified association of CCCTC-binding factor (CTCF) with Ahr promoter in mouse livers. Both MED1 and CTCF are validated conserved miR-122 targets. Furthermore, depletion of Ahr, Med1, or Ctcf in Mir122
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