Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11-12
pubmed:dateCreated
2009-12-16
pubmed:abstractText
We investigated miRNA expression changes associated with stress-induced premature senescence (SIPS) in primary cultures of human diploid fibroblast (HDF) and human trabecular meshwork (HTM) cells. Twenty-five miRNAs were identified by miRNA microarray analysis and their changes in expression were validated by TaqMan real-time RT-PCR in three independent cell lines of HTM and HDF. SIPS in both HTM and HDF cell types was associated with significant down-regulation of four members of the miR-15 family and five miRNAs of the miR-106b family located in the oncogenic clusters miR-17-92, miR-106a-363, and miR-106b-25. SIPS was also associated with up-regulation of two miRNAs (182 and 183) from the miR-183-96-182 cluster. Transfection with miR-106a agomir inhibited the up-regulation of p21(CDKN1A) associated with SIPS while transfection with miR-106a antagomir led to increased p21(CDKN1A) expression in senescent cells. In addition, we identified retinoic acid receptor gamma (RARG) as a target of miR-182 and showed that this protein was down-regulated during SIPS in HDF and HTM cells. These results suggest that changes in miRNA expression might contribute to phenotypic alterations of senescent cells by modulating the expression of key regulatory proteins such as p21(CDKN1A) as well as by targeting genes that are down-regulated in senescent cells such as RARG.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1872-6216
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
130
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
731-41
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed-meshheading:19782699-Adolescent, pubmed-meshheading:19782699-Adult, pubmed-meshheading:19782699-Cell Aging, pubmed-meshheading:19782699-Cell Line, pubmed-meshheading:19782699-Child, pubmed-meshheading:19782699-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:19782699-Female, pubmed-meshheading:19782699-Fibroblasts, pubmed-meshheading:19782699-Gene Expression, pubmed-meshheading:19782699-Gene Expression Regulation, pubmed-meshheading:19782699-Humans, pubmed-meshheading:19782699-Male, pubmed-meshheading:19782699-MicroRNAs, pubmed-meshheading:19782699-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:19782699-Oxidative Stress, pubmed-meshheading:19782699-Phenotype, pubmed-meshheading:19782699-Receptors, Retinoic Acid, pubmed-meshheading:19782699-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19782699-Trabecular Meshwork, pubmed-meshheading:19782699-Transfection
pubmed:articleTitle
Alterations in microRNA expression in stress-induced cellular senescence.
pubmed:affiliation
Department of Ophthalmology, Duke University, Durham, NC 27710, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural