Evidence map›Paper›PMID 22022355›Full record

ArticlePloS one2011

Cellular stress induced alterations in microRNA let-7a and let-7b expression are dependent on p53.

Anthony D Saleh, Jason E Savage, Liu Cao, Benjamin P Soule, David Ly, William DeGraff, Curtis C Harris, James B Mitchell, Nicole L Simone

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

58 citing papers in PubMed, 98 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Role of p53 in Regulating Radiation Responses.Life (Basel, Switzerland) · 2022
    Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. A Perspective of Epigenetic Regulation in Radiotherapy.Frontiers in cell and developmental biology · 2021
    Review
  13. Article
  14. Article
  15. Review
  16. MicroRNA Networks Modulate Oxidative Stress in Cancer.International journal of molecular sciences · 2019
    Review
  17. Review
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

  • Erratum issued
  • Erratum issued
5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Anthony D SalehRadiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
Jason E Savage
Liu Cao
Benjamin P Soule
David Ly
William DeGraff
Curtis C Harris
James B Mitchell
Nicole L Simone
National Institutes of Health · USNational Cancer Institute · US

Funding

Modulation of Therapeutic ResponseZIASC006321 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI MITCHELL, JAMES · 2009 to 2025
$17.3M
Intramural NIH HHS
6 · The paper itself

Abstract

Genotoxic stressors, such as radiation, induce cellular damage that activates pre-programmed repair pathways, some of which involve microRNAs (miRNA) that alter gene expression. The let-7 family of miRNA regulates multiple cellular processes including cell division and DNA repair pathways. However, the role and mechanism underlying regulation of let-7 genes in response to stress have yet to be elucidated. In this study we demonstrate that let-7a and let-7b expression decreases significantly following exposure to agents that induce stress including ionizing radiation. This decrease in expression is dependent on p53 and ATM in vitro and is not observed in a p53(-/-) colon cancer cell line (HCT116) or ATM(-/-) human fibroblasts. Chromatin Immunoprecipitation (ChIP) analysis showed p53 binding to a region upstream of the let-7 gene following radiation exposure. Luciferase transient transfections demonstrated that this p53 binding site is necessary for radiation-induced decreases in let-7 expression. A radiation-induced decrease in let-7a and let-7b expression is also observed in radiation-sensitive tissues in vivo and correlates with altered expression of proteins in p53-regulated pro-apoptotic signaling pathways. In contrast, this decreased expression is not observed in p53 knock-out mice suggesting that p53 directly repress let-7 expression. Exogenous expression of let-7a and let-7b increased radiation-induced cytotoxicity in HCT116 p53(+/+) cells but not HCT116 p53(-/-) cells. These results are the first demonstration of a mechanistic connection between the radiation-induced stress response and the regulation of miRNA and radiation-induced cytotoxicity and suggest that this process may be a molecular target for anticancer agents.

Indexed as

Gene Expression Regulation, NeoplasticOxidative StressAnimalsApoptosis Regulatory ProteinsAtaxia Telangiectasia Mutated Proteinsbcl-2-Associated X ProteinCell Cycle ProteinsDNA-Binding ProteinsDNA DamageEnhancer Elements, GeneticHCT116 CellsHumansMiceMice, Inbred C57BLMicroRNAsPhosphorylationApoptosis Regulatory ProteinsAtaxia Telangiectasia Mutated ProteinsATM protein, humanAtm protein, mousebcl-2-Associated X ProteinCell Cycle ProteinsDNA-Binding ProteinsMicroRNAsmirnlet7 microRNA, humanmirnlet7 microRNA, mouseProtein Serine-Threonine KinasesPUMA protein, mouseTumor Suppressor Protein p53Tumor Suppressor Proteins

Identifiers

PMID22022355
PMCPMC3191136
OpenAlexW2139246040

What OpenQuestion holds

Textmetadata
LicenceCC0
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.