Evidence map›Paper›PMID 26300493›Full record

ArticleCancer letters2015

NRF2/miR-140 signaling confers radioprotection to human lung fibroblasts.

Nadire Duru, Ramkishore Gernapudi, Yongshu Zhang, Yuan Yao, Pang-Kuo Lo, Benjamin Wolfson, Qun Zhou

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

Article in Cancer letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

25 citing papers in PubMed, 37 citations in OpenAlex.

  1. Review
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  7. Roles of NRF2 in DNA damage repair.Cellular oncology (Dordrecht, Netherlands) · 2023
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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

7 authors at 2 institutions in 1 country.

Nadire DuruDepartment of Biochemistry and Molecular Biology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Ramkishore GernapudiDepartment of Biochemistry and Molecular Biology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Yongshu ZhangDepartment of Biochemistry and Molecular Biology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Yuan YaoDepartment of Biochemistry and Molecular Biology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Pang-Kuo LoDepartment of Biochemistry and Molecular Biology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Benjamin WolfsonDepartment of Biochemistry and Molecular Biology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Qun ZhouDepartment of Biochemistry and Molecular Biology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: qzhou@som.umaryland.edu.
U-M Rogel Cancer CenterUniversity of Maryland, Baltimore · US

Funding

Training Grant in Cancer BiologyT32CA154274 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI Toni M Antalis, CURT I CIVIN · 2011 to 2026
$6.8M
miR-140 and Breast Cancer PreventionR01CA163820 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI ZHOU, QUN · 2012 to 2016
$1.6M
Shikonin and Nrf2 ChemopreventionR01CA157779 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI ZHOU, QUN · 2013 to 2017
$1.4M
NCI NIH HHS R01 CA157779NCI NIH HHS R01 CA157779A1NCI NIH HHS R01 CA163820NCI NIH HHS R01 CA163820A1NCI NIH HHS T32 CA154274
6 · The paper itself

Abstract

Breast and lung cancer patients who are treated with radiotherapy often have severe side effects, including radiation-induced lung damage and secondary cancers. Activation of the NRF2 pathway is a well-known mechanism that protects cells against radiation induced oxidative stress, but its role in radiation-induced lung damage is not well understood. Using human lung fibroblasts (HLFs) we found that ionizing radiation (IR) leads to BRCA1-dependent activation of NRF2 through the inhibition of KEAP1 function, promoting the nuclear accumulation of NRF2, and activating critical radioprotective mechanisms. We discovered that NRF2 directly binds to the miR-140 promoter and increases its expression in response to IR treatment. Gain and loss of function studies further showed the ability of miR-140 to regulate lung fibroblast self-renewal upon irradiation, a potential mechanism to contribute to the regulation of DNA repair. We verified our in vitro findings using primary lung fibroblast cultures from wild type and Nrf2 (KO) mice. Using these models we showed that IR induces overexpression of Brca1, Nrf2 and miR-140 in lung tissue after irradiation. These data reveal a novel radioprotective mechanism in which IR promotes NRF2 nuclear translocation and subsequent activation of miR-140 transcription in HLFs.

Indexed as

Active Transport, Cell NucleusAnimalsBRCA1 ProteinCell LineCell Self RenewalFibroblastsGene Expression RegulationHumansIntracellular Signaling Peptides and ProteinsKelch-Like ECH-Associated Protein 1LungMiceMice, Inbred C57BLMice, KnockoutMicroRNAsNF-E2-Related Factor 2BRCA1 ProteinBRCA1 protein, humanIntracellular Signaling Peptides and ProteinsKEAP1 protein, humanKelch-Like ECH-Associated Protein 1MicroRNAsMirn140 microRNA, humanNFE2L2 protein, humanNF-E2-Related Factor 2BRCA1miR-140NRF2Radiation-induced injuryRadioprotection

Identifiers

PMID26300493
PMCPMC4892935
OpenAlexW2154330794

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.