Evidence map›Paper›PMID 24735967›Full record

ArticleBlood2014

Premalignant PTEN-deficient thymocytes activate microRNAs miR-146a and miR-146b as a cellular defense against malignant transformation.

Megan L Burger, Ling Xue, Yuefang Sun, Chulho Kang, Astar Winoto

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

Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

15 citing papers in PubMed, 22 citations in OpenAlex.

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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 1 institution in 1 country.

Megan L BurgerDepartment of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley, CA.
Ling XueDepartment of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley, CA.
Yuefang SunDepartment of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley, CA.
Chulho KangDepartment of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley, CA.
Astar WinotoDepartment of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley, CA.
University of California, Berkeley · US

Funding

PROGRAMMED CELL DEATH IN NORMAL AND MALIGNANT T CELLSR01CA066236 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI WINOTO, ASTAR · 1995 to 2014
$4.7M
The Mechanism of Nur77 and Nor1 Induced Apoptosis Through Interaction with Bcl2F31CA168007 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI BURGER, MEGAN LINN · 2013 to 2014
$66k
NCI NIH HHS CA168007NCI NIH HHS CA66236NCI NIH HHS F31 CA168007NCI NIH HHS R01 CA066236
6 · The paper itself

Abstract

Cancer develops by a multistep process during which cells acquire characteristics that allow them to evade apoptosis and proliferate unchecked. Sequential acquisition of genetic alterations drives this process but also causes cellular stress, frequently prompting cells to enter a premalignant period during which they mount a defense against transformation. T cell-specific deletion of the tumor suppressor PTEN in mice induces premalignancy in the thymus and development of CD4(+) T-cell lymphomas in the periphery. Here we sought to identify factors mediating the cellular defense against transformation during the premalignant period. We identified several microRNAs upregulated specifically in premalignant thymocytes, including miR-146a, miR-146b, and the miR-183/96/182 cluster. CD4-driven T cell-specific transgenic overexpression of mir-146a and mir-146b significantly delayed PTEN-deficient lymphomagenesis and delayed c-myc oncogene induction, a key driver of transformation in PTEN-deficient T-cell malignancies. We found that miR-146a and miR-146b targeting of Traf6 attenuates TCR signaling in the thymus and inhibits downstream NF-κB-dependent induction of c-myc. Additionally, c-myc repression in mature CD4 T cells by miR-146b impaired TCR-mediated proliferation. Hence, we have identified 2 miRNAs that are upregulated as part of the cellular response against transformation that, when overrepresented, can effectively inhibit progression to malignancy in the context of PTEN deficiency.

Indexed as

AnimalsCD4-Positive T-LymphocytesCell ProliferationCell Transformation, NeoplasticGene Expression Regulation, NeoplasticLymphoma, T-CellMiceMice, KnockoutMicroRNAsMultigene FamilyProto-Oncogene Proteins c-mycPTEN PhosphohydrolaseReceptors, Antigen, T-CellRNA, NeoplasmSignal TransductionThymocytesMicroRNAsMirn146 microRNA, mouseMyc protein, mouseProto-Oncogene Proteins c-mycPTEN PhosphohydrolasePten protein, mouseReceptors, Antigen, T-CellRNA, NeoplasmTNF Receptor-Associated Factor 6

Identifiers

PMID24735967
PMCPMC4073325
OpenAlexW2129610269

What OpenQuestion holds

Textmetadata
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.