Evidence map›Paper›PMID 27770549›Full record

ArticleHepatology (Baltimore, Md.)2017

Long noncoding RNA MEG3 induces cholestatic liver injury by interaction with PTBP1 to facilitate shp mRNA decay.

Li Zhang, Zhihong Yang, Jocelyn Trottier, Olivier Barbier, Li Wang

Open access · bronzeAbstract read
In one paragraph

Article in Hepatology (Baltimore, Md.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed, 1 pooled it
7.9field-weighted citation impact, top 2% 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

115 citing papers in PubMed, 1 synthesis or guideline pooled it, 185 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Advances in the Regulation of Lipid Metabolism by Non-Coding RNAs.Animals : an open access journal from MDPI · 2025
    Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. PTBP1 as a potential regulator of disease.Molecular and cellular biochemistry · 2024
    Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Article

55 more citing papers are in PubMed but not listed here.

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

5 authors at 3 institutions in 3 countries.

Li ZhangDepartment of Physiology and Neurobiology and Institute for Systems Genomics, University of Connecticut, Storrs, CT.
Zhihong YangDepartment of Physiology and Neurobiology and Institute for Systems Genomics, University of Connecticut, Storrs, CT.
Jocelyn TrottierLaboratory of Molecular Pharmacology, CHU-Québec Research Centre and Faculty of Pharmacy, Laval University, Québec, Canada.
Olivier BarbierLaboratory of Molecular Pharmacology, CHU-Québec Research Centre and Faculty of Pharmacy, Laval University, Québec, Canada.
Li WangDepartment of Physiology and Neurobiology and Institute for Systems Genomics, University of Connecticut, Storrs, CT.
Université Laval · CAUniversity of Connecticut · USVA Connecticut Healthcare System · US

Funding

Yale Liver CenterP30DK034989 · NIDDK · YALE UNIVERSITY · PI WAJAHAT Zafar MEHAL · 1986 to 2026
$31.1M
SHP-regulation of Lipid and Lipoprotein MetabolismR01DK080440 · NIDDK · UNIVERSITY OF UTAH · PI WANG, LI · 2008 to 2015
$2.3M
LncRNA as a New Mediator of Bile Acid HomeostasisR01DK104656 · NIDDK · UNIVERSITY OF CONNECTICUT STORRS · PI WANG, LI · 2015 to 2018
$1.7M
Molecular Basis of Cancer Cell Metabolic ReprogrammingR01ES025909 · NIEHS · UNIVERSITY OF CONNECTICUT STORRS · PI WANG, LI · 2015 to 2017
$1.0M
Long noncoding RNAs in alcoholic liver diseaseR21AA024935 · NIAAA · INDIANA UNIVERSITY INDIANAPOLIS · PI LIANGPUNSAKUL, SUTHAT, WANG, LI · 2016 to 2017
$431k
Alcohol, nuclear receptor signaling, and circadian clocksR21AA022482 · NIAAA · UNIVERSITY OF CONNECTICUT STORRS · PI WANG, LI · 2015 to 2016
$415k
Circadian Clock Regulation of Alcoholic Liver DiseaseI01BX002634 · VA · VA CONNECTICUT HEALTHCARE SYSTEM · PI WANG, LI · 2016 to 2019
–
BLRD VA I01 BX002634NIAAA NIH HHS R21 AA022482NIAAA NIH HHS R21 AA024935NIDDK NIH HHS P30 DK034989NIDDK NIH HHS R01 DK080440NIDDK NIH HHS R01 DK104656NIEHS NIH HHS R01 ES025909
6 · The paper itself

Abstract

Bile acids (BAs) play critical physiological functions in cholesterol homeostasis, and deregulation of BA metabolism causes cholestatic liver injury. The long noncoding RNA maternally expressed gene 3 (MEG3) was recently shown as a potential tumor suppressor; however, its basic hepatic function remains elusive. Using RNA pull-down with biotin-labeled sense or anti-sense MEG 3RNA followed by mass spectrometry, we identified RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1) as a MEG3 interacting protein and validated their interaction by RNA immunoprecipitation (RIP). Bioinformatics analysis revealed putative binding sites for PTBP1 within the coding region (CDS) of small heterodimer partner (SHP), a key repressor of BA biosynthesis. Forced expression of MEG3 in hepatocellular carcinoma cells guided and facilitated PTBP1 binding to the Shp CDS, resulting in Shp mRNA decay. Transient overexpression of MEG3 RNA in vivo in mouse liver caused rapid Shp mRNA degradation and cholestatic liver injury, which was accompanied by the disruption of BA homeostasis, elevation of liver enzymes, as well as dysregulation of BA synthetic enzymes and metabolic genes. Interestingly, RNA sequencing coupled with quantitative PCR (qPCR) revealed a drastic induction of MEG3 RNA in Shp

conclusionMEG3 causes cholestasis by serving as a guide RNA scaffold to recruit PTBP1 to destabilize Shp mRNA. SHP in turn represses CREB-mediated activation of MEG3 expression in a feedback-regulatory fashion. (Hepatology 2017;65:604-615).

Indexed as

AnimalsBinding SitesCells, CulturedCholestasisDisease Models, AnimalDown-RegulationHepatocytesHep G2 CellsHeterogeneous-Nuclear RibonucleoproteinsHumansLiverMiceMice, Inbred C57BLMice, KnockoutPolypyrimidine Tract-Binding ProteinPromoter Regions, GeneticHeterogeneous-Nuclear RibonucleoproteinsMEG3 non-coding RNA, mousePolypyrimidine Tract-Binding ProteinPtbp1 protein, mouseRNA, Long Noncoding

Identifiers

PMID27770549
PMCPMC5258819
OpenAlexW2560973135

What OpenQuestion holds

Textmetadata
LicenceTDM
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.