Evidence map›Paper›PMID 26055138›Full record

ArticleGastroenterology2015

MicroRNA214 Is Associated With Progression of Ulcerative Colitis, and Inhibition Reduces Development of Colitis and Colitis-Associated Cancer in Mice.

Christos Polytarchou, Daniel W Hommes, Tiziana Palumbo, Maria Hatziapostolou, Marina Koutsioumpa, Georgios Koukos, Andrea E van der Meulen-de Jong, Angelos Oikonomopoulos, Welmoed K van Deen, Christina Vorvis and 9 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed, 3 pooled it
6.9field-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

87 citing papers in PubMed, 3 syntheses or guidelines pooled it, 126 citations in OpenAlex.

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  20. MicroRNAs in Inflammatory Bowel Disease and Its Complications.International journal of molecular sciences · 2022
    Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 4 institutions in 2 countries.

Christos PolytarchouCenter for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Daniel W HommesDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands; Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Tiziana PalumboCenter for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Maria HatziapostolouCenter for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Marina KoutsioumpaCenter for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Georgios KoukosCenter for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Andrea E van der Meulen-de JongDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
Angelos OikonomopoulosCenter for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Welmoed K van DeenDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands; Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Christina VorvisCenter for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Oksana B SerebrennikovaMolecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts.
Eleni BirliCenter for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Jennifer ChoiCenter for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Lin ChangGail and Gerard Oppenheimer Family Center of Neurobiology of Stress, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Peter A AntonCenter for HIV Prevention Research, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Philip N TsichlisMolecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts.
Charalabos PothoulakisCenter for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Hein W VerspagetDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
Dimitrios IliopoulosCenter for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California. Electronic address: diliopoulos@mednet.ucla.edu.
University of California, Los Angeles · USLeiden University Medical Center · NLMolecular Oncology (United States) · USTufts Medical Center · US

Funding

UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
Mechanisms of Neurotensin in Intestinal InflammationR01DK060729 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI POTHOULAKIS, CHARALABOS · 2002 to 2017
$5.0M
NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1TR000124NIDDK NIH HHS P30 DK041301NIDDK NIH HHS R01 DK060729NIDDK NIH HHS R01 DK60729
6 · The paper itself

Abstract

BACKGROUND &

aimsPersistent activation of the inflammatory response contributes to the development of inflammatory bowel diseases, which increase the risk of colorectal cancer. We aimed to identify microRNAs that regulate inflammation during the development of ulcerative colitis (UC) and progression to colitis-associated colon cancer (CAC).

methodsWe performed a quantitative polymerase chain reaction analysis to measure microRNAs in 401 colon specimens from patients with UC, Crohn's disease, irritable bowel syndrome, sporadic colorectal cancer, or CAC, as well as subjects without these disorders (controls); levels were correlated with clinical features and disease activity of patients. Colitis was induced in mice by administration of dextran sodium sulfate (DSS), and carcinogenesis was induced by addition of azoxymethane; some mice also were given an inhibitor of microRNA214 (miR214).

resultsA high-throughput functional screen of the human microRNAome found that miR214 regulated the activity of nuclear factor-κB. Higher levels of miR214 were detected in colon tissues from patients with active UC or CAC than from patients with other disorders or controls and correlated with disease progression. Bioinformatic and genome-wide profile analyses showed that miR214 activates an inflammatory response and is amplified through a feedback loop circuit mediated by phosphatase and tensin homolog (PTEN) and PDZ and LIM domain 2 (PDLIM2). Interleukin-6 induced signal transducer and activator of transcription 3 (STAT3)-mediated transcription of miR214. A miR214 chemical inhibitor blocked this circuit and reduced the severity of DSS-induced colitis in mice, as well as the number and size of tumors that formed in mice given azoxymethane and DSS. In fresh colonic biopsy specimens from patients with active UC, the miR214 inhibitor reduced inflammation by increasing levels of PDLIM2 and PTEN.

conclusionsInterleukin-6 up-regulates STAT3-mediated transcription of miR214 in colon tissues, which reduces levels of PDLIM2 and PTEN, increases phosphorylation of AKT, and activates nuclear factor-κB. The activity of this circuit correlates with disease activity in patients with UC and progression to colorectal cancer.

Indexed as

RNAi TherapeuticsAdaptor Proteins, Signal TransducingAnimalsAzoxymethaneBiomarkers, TumorCase-Control StudiesCell LineColitis, UlcerativeColonColonic NeoplasmsDextran SulfateDisease Models, AnimalDisease ProgressionGene Expression Regulation, NeoplasticHumansInflammation MediatorsAdaptor Proteins, Signal TransducingAzoxymethaneBiomarkers, TumorDextran SulfateInflammation MediatorsInterleukin-6interleukin-6, mouseLIM Domain ProteinsMicroRNAsMIRN214 microRNA, humanMirn214 microRNA, mouseNF-kappa BPdlim2 protein, mouseProto-Oncogene Proteins c-aktPTEN PhosphohydrolasePten protein, mouseStat3 protein, mouseSTAT3 Transcription FactorChronic InflammationIBD ProgressionIL6Mouse Model

Identifiers

PMID26055138
PMCPMC4584179
OpenAlexW1917406468

What OpenQuestion holds

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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.