Linked Life Data

17110380

Source:http://linkedlifedata.com/resource/pubmed/id/17110380

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-1-8
pubmed:abstractText
Deregulation of micro-RNAs (miRNAs) is emerging as a major aspect of cancer etiology because their capacity to direct the translation and stability of targeted transcripts can dramatically influence cellular physiology. To explore the potential of exogenously applied miRNAs to suppress oncogenic proteins, the ERBB oncogene family was chosen with a bioinformatics search identifying targeting seed sequences for miR-125a and miR-125b within the 3'-untranslated regions of both ERBB2 and ERBB3. Using the human breast cancer cell line SKBR3 as a model for ERBB2 and ERBB3 dependence, infection of these cells with retroviral constructs expressing either miR-125a or miR-125b resulted in suppression of ERBB2 and ERBB3 at both the transcript and protein level. Luciferase constructs containing the 3' 3'-untranslated regions of ERBB2 and ERBB3 demonstrated approximately 35% less activity in miR-125a- and miR-125b-expressing cells relative to controls. Additionally, phosphorylation of ERK1/2 and AKT was suppressed in SKBR3 cells overexpressing either miR-125a or miR-125b. Consistent with suppression of both ERBB2 and ERBB3 signaling, miR-125a-or miR-125b-overexpressing SKBR3 cells were impaired in their anchorage-dependent growth and exhibited reduced migration and invasion capacities. Parallel studies performed on MCF10A cells demonstrated that miR-125a or miR-125b overexpression produced only marginal influences on the growth and migration of these non-transformed human mammary epithelial cells. These results illustrate the feasibility of using miRNAs as a therapeutic strategy to suppress oncogene expression and function.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1479-86
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17110380-Breast Neoplasms, pubmed-meshheading:17110380-Cell Adhesion, pubmed-meshheading:17110380-Cell Division, pubmed-meshheading:17110380-Cell Line, Tumor, pubmed-meshheading:17110380-Cell Movement, pubmed-meshheading:17110380-Epithelial Cells, pubmed-meshheading:17110380-Gene Expression Regulation, Neoplastic, pubmed-meshheading:17110380-Gene Therapy, pubmed-meshheading:17110380-Humans, pubmed-meshheading:17110380-MAP Kinase Signaling System, pubmed-meshheading:17110380-MicroRNAs, pubmed-meshheading:17110380-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:17110380-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:17110380-Proto-Oncogene Proteins c-akt, pubmed-meshheading:17110380-Receptor, erbB-2, pubmed-meshheading:17110380-Receptor, erbB-3, pubmed-meshheading:17110380-Retroviridae
pubmed:year
2007
pubmed:articleTitle
Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b.
pubmed:affiliation
Buck Institute for Age Research, Novato, California 94945, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural