Evidence map›Paper›PMID 32222775›Full record

ArticleArchives of toxicology2020

Long noncoding RNA LINC00844-mediated molecular network regulates expression of drug metabolizing enzymes and nuclear receptors in human liver cells.

Dongying Li, Leihong Wu, Bridgett Knox, Si Chen, William H Tolleson, Fang Liu, Dianke Yu, Lei Guo, Weida Tong, Baitang Ning

Open access · greenAbstract read
In one paragraph

Article in Archives of toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.0field-weighted citation impact, top 28% 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

16 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. LncRNAiScience · 2025
    Article
  3. Article
  4. Article
  5. Review
  6. Novel Approaches to Characterize Individual Drug Metabolism and Advance Precision Medicine.Drug metabolism and disposition: the biological fate of chemicals · 2023
    Review
  7. Review
  8. Review
  9. miRNA-486-5p: signaling targets and role in non-malignant disease.Cellular and molecular life sciences : CMLS · 2022
    Review
  10. Article
  11. Article
  12. Non-coding RNA crosstalk with nuclear receptors in liver disease.Biochimica et biophysica acta. Molecular basis of disease · 2021
    Review
  13. Article
  14. Article
  15. Review
  16. Review
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

10 authors at 3 institutions in 2 countries.

Dongying LiNational Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), 3900 NCTR Road, HFT100, Jefferson, AR, 72079, USA.
Leihong WuNational Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), 3900 NCTR Road, HFT100, Jefferson, AR, 72079, USA.
Bridgett KnoxNational Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), 3900 NCTR Road, HFT100, Jefferson, AR, 72079, USA.
Si ChenNational Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), 3900 NCTR Road, HFT100, Jefferson, AR, 72079, USA.
William H TollesonNational Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), 3900 NCTR Road, HFT100, Jefferson, AR, 72079, USA.
Fang LiuNational Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), 3900 NCTR Road, HFT100, Jefferson, AR, 72079, USA.
Dianke YuSchool of Public Health, Qingdao University, Qingdao, China.
Lei GuoNational Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), 3900 NCTR Road, HFT100, Jefferson, AR, 72079, USA.
Weida TongNational Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), 3900 NCTR Road, HFT100, Jefferson, AR, 72079, USA.
Baitang NingNational Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), 3900 NCTR Road, HFT100, Jefferson, AR, 72079, USA. baitang.ning@fda.hhs.gov.
United States Food and Drug Administration · USNational Center for Toxicological Research · USQingdao University · CN

Funding

Intramural FDA HHS FD999999U.S. Food and Drug Administration E0753201
6 · The paper itself

Abstract

Noncoding RNAs, such as long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), regulate gene expression in many physiological and pathological processes, including drug metabolism. Drug metabolizing enzymes (DMEs) are critical components in drug-induced liver toxicity. In this study, we used human hepatic HepaRG cells treated with 5 or 10 mM acetaminophen (APAP) as a model system and identified LINC00844 as a toxicity-responsive lncRNA. We analyzed the expression profiles of LINC00844 in different human tissues. In addition, we examined the correlations between the levels of LINC00844 and those of key DMEs and nuclear receptors (NRs) for APAP metabolism in humans. Our results showed that lncRNA LINC00844 is enriched in the liver and its expression correlates positively with mRNA levels of CYP3A4, CYP2E1, SULT2A1, pregnane X receptor (PXR), and hepatocyte nuclear factor (HNF) 4α. We demonstrated that LINC00844 regulates the expression of these five genes in HepaRG cells using gain- and loss-of-function assays. Further, we discovered that LINC00844 is localized predominantly in the cytoplasm and acts as an hsa-miR-486-5p sponge, via direct binding, to protect SULT2A1 from miRNA-mediated gene silencing. Our data also demonstrated a functional interaction between LINC00844 and hsa-miR-486-5p in regulating DME and NR expression in HepaRG cells and primary human hepatocytes. We depicted a LINC00844-mediated regulatory network that involves miRNA and NRs and influences DME expression in response to APAP toxicity.

Indexed as

AcetaminophenCell LineCytochrome P-450 CYP2E1Cytochrome P-450 CYP3AHepatocytesHep G2 CellsHumansInactivation, MetabolicLiverMetabolic Clearance RateMicroRNAsPharmaceutical PreparationsPregnane X ReceptorReceptors, Cytoplasmic and NuclearRNA, Long NoncodingRNA, MessengerAcetaminophenCytochrome P-450 CYP2E1Cytochrome P-450 CYP3AMicroRNAsMIRN486 microRNA, humanNR1I2 protein, humanPharmaceutical PreparationsPregnane X ReceptorReceptors, Cytoplasmic and NuclearRNA, Long NoncodingRNA, MessengerAcetaminophenDrug metabolismLINC00844Liver toxicityLong noncoding RNAmicroRNA

Identifiers

PMID32222775
PMCPMC7773225
OpenAlexW3013906686

What OpenQuestion holds

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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.