Evidence map›Paper›PMID 28951593›Full record

ArticleScientific reports2017

MicroRNA regulation of CYP 1A2, CYP3A4 and CYP2E1 expression in acetaminophen toxicity.

Pritmohinder Gill, Sudeepa Bhattacharyya, Sandra McCullough, Lynda Letzig, Prasun J Mishra, Chunqiao Luo, Harsh Dweep, Laura James

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
7.1field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 62 citations in OpenAlex.

  1. DICER-driven regulation of lipid metabolism and macrophage-adipocyte crosstalk in partial lipodystrophy.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026
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  8. Novel Approaches to Characterize Individual Drug Metabolism and Advance Precision Medicine.Drug metabolism and disposition: the biological fate of chemicals · 2023
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  12. Hepatotoxicity due to herbal dietary supplements: Past, present and the future.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2022
    Review
  13. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Pritmohinder GillDepartment of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, 72202, USA. PSGill@uams.edu.
Sudeepa BhattacharyyaDepartment of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, 72202, USA.
Sandra McCulloughDepartment of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, 72202, USA.
Lynda LetzigDepartment of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, 72202, USA.
Prasun J MishraDepartment of Biochemical and Cellular Pharmacology, Genentech, 1, DNA Way, South San Francisco, California, 94080, USA.
Chunqiao LuoArkansas Children's Research Institute, Little Rock, AR, 72202, USA.
Harsh DweepThe Wistar Institute, 3601 Spruce St, Philadelphia, Pennsylvania, 19104, USA.
Laura JamesDepartment of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, 72202, USA.
University of Arkansas for Medical Sciences · USArkansas Children's Hospital · USThe Wistar Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

MicroRNAs (miRNAs) that regulate the cytochrome P-450 isoforms involved in acetaminophen (APAP) toxicity were examined in HepaRG cells treated with APAP (20 mM). In-vitro studies found that APAP protein adducts were increased at 1 h, followed by ALT increases at 12 and 24 h. CYP1A2, CYP3A4 and CYP2E1 mRNA levels were decreased, while miRNAs were increased for miR-122-5p, miR-378a-5p, miR-27b-3p at 6 h and miR-125b-5p at 12 h and miR-27b-3p at 24 h. Putative miRNA binding sites on the 3'UTRs of the CYPs were identified in-silico. Overexpression of miR-122-5p and miR-378a-5p in cells suppressed protein expression of CYP1A2, CYP3A4 and CYP2E1. Luciferase reporter assays confirmed the interaction between miR-122 and the 3'UTR of the CYP1A2 and CYP3A4. Thus, the in-vitro experiments showed that miR-122-5p and miR-378a-5p upregulation were associated with translational repression of CYPs. Serum samples of children with APAP overdose had significant elevation of miR-122-5p, miR-378a-5p, miR-125b-5p and miR-27b-3p, compared to healthy controls and receiver operator curves of the miRNAs had AUCs of 91 to 100%. Collectively, the data suggest that miRNA elevations in APAP toxicity represent a regulatory response to modify CYP1A2, CYP3A4 and CYP2E1 translation due to cellular stress and injury.

Indexed as

3' Untranslated RegionsAcetaminophenAdolescentBinding SitesCell LineChildChild, PreschoolCytochrome P-450 CYP1A2Cytochrome P-450 CYP2E1Cytochrome P-450 CYP3ADrug OverdoseFemaleHepatocytesHumansMaleMicroRNAs3' Untranslated RegionsAcetaminophenCYP1A2 protein, humanCYP3A4 protein, humanCytochrome P-450 CYP1A2Cytochrome P-450 CYP2E1Cytochrome P-450 CYP3AMicroRNAs

Identifiers

PMID28951593
PMCPMC5614957
OpenAlexW2754527362

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.