Evidence map›Paper›PMID 33893298›Full record

ArticleNature communications2021

MicroRNA-146a limits tumorigenic inflammation in colorectal cancer.

Lucien P Garo, Amrendra K Ajay, Mai Fujiwara, Galina Gabriely, Radhika Raheja, Chantal Kuhn, Brendan Kenyon, Nathaniel Skillin, Ryoko Kadowaki-Saga, Shrishti Saxena and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 2 pooled it
11.9field-weighted citation impact, top 1% 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

83 citing papers in PubMed, 2 syntheses or guidelines pooled it, 124 citations in OpenAlex.

  1. Pooled it
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  5. miR-146a mimic therapy protects against platelet-mediated thrombosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
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23 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

11 authors at 1 institution in 1 country.

Lucien P GaroAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-5369-1958
Amrendra K Ajay *Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-2790-5726
Mai Fujiwara *Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-5540-182X
Galina GabrielyAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Radhika RahejaAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Chantal KuhnAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Brendan KenyonAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Nathaniel SkillinAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-1424-9037
Ryoko Kadowaki-SagaAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Shrishti SaxenaAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Gopal MurugaiyanAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. mgopal@rics.bwh.harvard.edu.ORCID 0000-0003-0439-1363
Brigham and Women's Hospital · US

Funding

MICRORNA CONTROL OF INFLAMMATORY AND REGULATORY T CELLS IN CENTRAL NERVOUS SYSTEM AUTOIMMUNITYR01AI127853 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI GOPAL, MURUGAIYAN · 2017 to 2021
$2.2M
The pathogenic role of miR-92a in the regulation of T helper cell responses in EAE and MSR01AI151953 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI GOPAL, MURUGAIYAN · 2020 to 2024
$2.1M
MicroRNA control of tumor-promoting inflammation in colon cancerR01CA267479 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Murugaiyan Gopal · 2022 to 2026
$1.9M
Therapeutic targeting of PD1 signaling in inflammatory bowel diseaseR21AI175890 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI GOPAL, MURUGAIYAN · 2023 to 2024
$467k
Development of novel PD1 agonist therapeutic strategies for multiple sclerosisR21AI174047 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI GOPAL, MURUGAIYAN · 2023 to 2024
$442k
NCI NIH HHS R01 CA267479NIAID NIH HHS R01 AI127853NIAID NIH HHS R01 AI151953NIAID NIH HHS R21 AI174047NIAID NIH HHS R21 AI175890
6 · The paper itself

Abstract

Chronic inflammation can drive tumor development. Here, we have identified microRNA-146a (miR-146a) as a major negative regulator of colonic inflammation and associated tumorigenesis by modulating IL-17 responses. MiR-146a-deficient mice are susceptible to both colitis-associated and sporadic colorectal cancer (CRC), presenting with enhanced tumorigenic IL-17 signaling. Within myeloid cells, miR-146a targets RIPK2, a NOD2 signaling intermediate, to limit myeloid cell-derived IL-17-inducing cytokines and restrict colonic IL-17. Accordingly, myeloid-specific miR-146a deletion promotes CRC. Moreover, within intestinal epithelial cells (IECs), miR-146a targets TRAF6, an IL-17R signaling intermediate, to restrict IEC responsiveness to IL-17. MiR-146a within IECs further suppresses CRC by targeting PTGES2, a PGE2 synthesis enzyme. IEC-specific miR-146a deletion therefore promotes CRC. Importantly, preclinical administration of miR-146a mimic, or small molecule inhibition of the miR-146a targets, TRAF6 and RIPK2, ameliorates colonic inflammation and CRC. MiR-146a overexpression or miR-146a target inhibition represent therapeutic approaches that limit pathways converging on tumorigenic IL-17 signaling in CRC.

Indexed as

AnimalsCarcinogenesisCells, CulturedColitisColorectal NeoplasmsGene Expression Regulation, NeoplasticHumansInflammationInterleukin-17MiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMicroRNAsReceptor-Interacting Protein Serine-Threonine Kinase 2Signal TransductionInterleukin-17MicroRNAsMirn146 microRNA, mouseReceptor-Interacting Protein Serine-Threonine Kinase 2TNF Receptor-Associated Factor 6

Identifiers

PMID33893298
PMCPMC8065171
OpenAlexW3155666068

What Socratic 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 Socratic graph.