Evidence map›Paper›PMID 25990308›Full record

ArticleNature communications2015

The oncogenic microRNA miR-21 promotes regulated necrosis in mice.

Xiaodong Ma, Daniel J Conklin, Fenge Li, Zhongping Dai, Xiang Hua, Yan Li, Zijun Y Xu-Monette, Ken H Young, Wei Xiong, Marcin Wysoczynski and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 1 pooled it
3.9field-weighted citation impact, top 6% 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

61 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Role of circulating microRNAs in tetralogy of Fallot.Postepy w kardiologii interwencyjnej = Advances in interventional cardiology · 2025
    Article
  9. Review
  10. ExosomalInternational journal of biological sciences · 2025
    Article
  11. Article
  12. Review
  13. The Role of MicroRNAs in Pancreatitis Development and Progression.International journal of molecular sciences · 2023
    Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. Review

1 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

14 authors at 7 institutions in 2 countries.

Xiaodong MaDepartment of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
Daniel J ConklinDiabetes and Obesity Center, Department of Medicine, University of Louisville, 580 South Preston Street, Delia Baxter, Louisville, Kentucky 40202, USA.
Fenge LiDiabetes and Obesity Center, Department of Medicine, University of Louisville, 580 South Preston Street, Delia Baxter, Louisville, Kentucky 40202, USA.
Zhongping DaiFox Chase Cancer Center, Institute for Cancer Research, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111, USA.
Xiang HuaFox Chase Cancer Center, Institute for Cancer Research, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111, USA.
Yan LiDepartment of Surgery, School of Medicine, University of Louisville, Louisville, Kentucky 40202, USA.
Zijun Y Xu-MonetteDepartment of Hematopathology, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Ken H YoungDepartment of Hematopathology, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Wei XiongCancer Research Institute, Central South University, Changsha 410078, China.
Marcin WysoczynskiDiabetes and Obesity Center, Department of Medicine, University of Louisville, 580 South Preston Street, Delia Baxter, Louisville, Kentucky 40202, USA.
Srinivas D SithuDiabetes and Obesity Center, Department of Medicine, University of Louisville, 580 South Preston Street, Delia Baxter, Louisville, Kentucky 40202, USA.
Sanjay SrivastavaDiabetes and Obesity Center, Department of Medicine, University of Louisville, 580 South Preston Street, Delia Baxter, Louisville, Kentucky 40202, USA.
Aruni BhatnagarDiabetes and Obesity Center, Department of Medicine, University of Louisville, 580 South Preston Street, Delia Baxter, Louisville, Kentucky 40202, USA.
Yong LiDepartment of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
University of Louisville · USBaxter (United States) · USFox Chase Cancer Center · USThe University of Texas MD Anderson Cancer Center · USCentral South University · CNCleveland Clinic Lerner College of Medicine · USSouth China Normal University · CN

Funding

Project 5 - Metabolomic Analysis of AtherothrombosisP20GM103492 · NIGMS · UNIVERSITY OF LOUISVILLE · PI DEFILIPPIS, ANDREW · 2012 to 2017
$13.8M
TOXICITY OF 4-HYDROXYALKENALS IN HEARTR01HL055477 · NHLBI · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI BHATNAGAR, ARUNI · 1997 to 2015
$4.4M
Convergence of MicroRNAs and p53 Signaling in Multiple Myeloma: Environmental CoR01CA138688 · NCI · UNIVERSITY OF LOUISVILLE · PI LI, YONG · 2009 to 2017
$2.9M
Cardioprotective Mechanisms of Glutathione S-transferase PR01HL089380 · NHLBI · UNIVERSITY OF LOUISVILLE · PI CONKLIN, DANIEL JOSEPH · 2008 to 2012
$2.1M
Atherogenic Mechanisms of ArsenicR01ES017260 · NIEHS · UNIVERSITY OF LOUISVILLE · PI SRIVASTAVA, SANJAY · 2009 to 2013
$1.6M
Atherogenic mechanism of lipid peroxidation-derived aldehydesR01HL095593 · NHLBI · UNIVERSITY OF LOUISVILLE · PI SRIVASTAVA, SANJAY · 2010 to 2013
$1.5M
NCI NIH HHS R01 CA138688NHLBI NIH HHS HL95593NHLBI NIH HHS R01 HL055477NHLBI NIH HHS R01 HL089380NHLBI NIH HHS R01 HL095593NHLBI NIH HHS R01 HL89380NIEHS NIH HHS ES17260NIEHS NIH HHS R01 ES017260NIGMS NIH HHS P20 GM103492
6 · The paper itself

Abstract

MicroRNAs (miRNAs) regulate apoptosis, yet their role in regulated necrosis remains unknown. miR-21 is overexpressed in nearly all human cancer types and its role as an oncogene is suggested to largely depend on its anti-apoptotic action. Here we show that miR-21 is overexpressed in a murine model of acute pancreatitis, a pathologic condition involving RIP3-dependent regulated necrosis (necroptosis). Therefore, we investigate the role of miR-21 in acute pancreatitis injury and necroptosis. miR-21 deficiency protects against caerulein- or L-arginine-induced acute pancreatitis in mice. miR-21 inhibition using locked-nucleic-acid-modified oligonucleotide effectively reduces pancreatitis severity. miR-21 deletion is also protective in tumour necrosis factor-induced systemic inflammatory response syndrome. These data suggest that miRNAs are critical participants in necroptosis and miR-21 enhances cellular necrosis by negatively regulating tumour suppressor genes associated with the death-receptor-mediated intrinsic apoptosis pathway, and could be a therapeutic target for preventing pathologic necrosis.

Indexed as

Gene Expression Regulation, NeoplasticNecrosisAnimalsApoptosisArginineBone Marrow TransplantationCaspasesCeruletideFas Ligand Proteinfas ReceptorFemaleGenes, Tumor SuppressorImidazolesIndolesInflammationMaleArginineCaspasesCeruletideFas Ligand Proteinfas ReceptorImidazolesIndolesMicroRNAsMIRN21 microRNA, mousenecrostatin-1OligonucleotidesReceptor-Interacting Protein Serine-Threonine KinasesRipk3 protein, mouseTumor Necrosis Factor-alpha

Identifiers

PMID25990308
PMCPMC4440243
OpenAlexW2181313495

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.