Source:http://linkedlifedata.com/resource/pubmed/id/17554199
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
13
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pubmed:dateCreated |
2007-7-11
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pubmed:databankReference | |
pubmed:abstractText |
In a genome-wide screen for microRNAs regulated by the transcription factor encoded by the p53 tumor suppressor gene we found that after p53-activation the abundance of thirty-four miRNAs was significantly increased, whereas sixteen miRNAs were suppressed. The induction of miR-34a was most pronounced among all differential regulations. Also expression of the primary miR-34a transcript was induced after p53 activation and by DNA damage in a p53-dependent manner. p53 occupied an evolutionarily conserved binding site proximal to the first non-coding exon of miR-34a. Ectopic miR-34a induced apoptosis and a cell cycle arrest in the G1-phase, thereby suppressing tumor cell proliferation. Other p53-induced miRNAs identified here may also have tumor suppressive potential as they are known to suppress the anti-apoptotic factor Bcl2 (miR-15a/16) and the oncogenes RAS and HMGA2 (let-7a). Our results for the first time directly integrate the regulation of miRNA expression into the transcriptional network regulated by p53. siRNAs corresponding to p53-induced miRNAs may have potential as cancer therapeutic agents as RNA interference based therapies are currently emerging.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1551-4005
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1586-93
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pubmed:dateRevised |
2008-12-19
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pubmed:meshHeading |
pubmed-meshheading:17554199-Apoptosis,
pubmed-meshheading:17554199-Base Sequence,
pubmed-meshheading:17554199-Chromosome Mapping,
pubmed-meshheading:17554199-DNA Damage,
pubmed-meshheading:17554199-G1 Phase,
pubmed-meshheading:17554199-Gene Expression Regulation,
pubmed-meshheading:17554199-Humans,
pubmed-meshheading:17554199-MicroRNAs,
pubmed-meshheading:17554199-Molecular Sequence Data,
pubmed-meshheading:17554199-Sequence Analysis, RNA,
pubmed-meshheading:17554199-Tumor Cells, Cultured,
pubmed-meshheading:17554199-Tumor Suppressor Protein p53
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pubmed:year |
2007
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pubmed:articleTitle |
Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest.
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pubmed:affiliation |
Molecular Oncology, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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