Source:http://linkedlifedata.com/resource/pubmed/id/20736365
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
20
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pubmed:dateCreated |
2010-10-15
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pubmed:abstractText |
Expression profiling has identified metastasis-associated microRNAs (miRNA) but technical limitations hinder the discovery of metastasis-suppressing miRNAs. In this study, we sought metastasis-suppressing miRNAs by functional screening. Individual miRNAs were lentivirally introduced into metastatic MDA-MB-231 breast cancer cells and analyzed for effects on cell migration, a critical step in cancer metastasis. Among 486 miRNAs screened, 14 were identified that included all of the members of the miRNA-196 family (miR-196a1, miR-196a2, and miR-196b). Enforced expression of miR-196a1/2 or miR-196b abrogated in vitro invasion and in vivo spontaneous metastasis of breast cancer cells, indicating that members of the miR-196 family are potent metastasis suppressors. We found that miR-196 inhibited the expression of transcription factor HOXC8. Functional linkage was implied by small interfering RNA-mediated knockdown of HOXC8, which suppressed cell migration and metastasis, and by ectopic expression of HOXC8, which prevented the effects of miR-196 on cell migration and metastasis. Unlike other metastasis-associated miRNAs that have been described, the expressions of miR-196 were not correlated with breast cancer cell migration or the metastatic status of clinical breast tumor specimens. Instead, we detected an excellent correlation between the ratio of miR-196 to HOXC8 messages and the migratory behavior of breast cancer cell lines as well as the metastatic status of clinical samples. Our findings identify miRNA-196s as potent metastasis suppressors and reveal that the ratio of miR-196s to HOXC8 mRNA might be an indicator of the metastatic capability of breast tumors.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/CA093926,
http://linkedlifedata.com/resource/pubmed/grant/HL083335,
http://linkedlifedata.com/resource/pubmed/grant/R01 CA093926-08,
http://linkedlifedata.com/resource/pubmed/grant/R01 CA093926-09,
http://linkedlifedata.com/resource/pubmed/grant/R01 HL083335-03,
http://linkedlifedata.com/resource/pubmed/grant/R01 HL083335-04
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/HOXC8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/MIRN196 microRNA, human,
http://linkedlifedata.com/resource/pubmed/chemical/MicroRNAs,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1538-7445
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pubmed:author | |
pubmed:copyrightInfo |
©2010 AACR.
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
70
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7894-904
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pubmed:dateRevised |
2011-10-17
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pubmed:meshHeading |
pubmed-meshheading:20736365-Breast Neoplasms,
pubmed-meshheading:20736365-Cell Movement,
pubmed-meshheading:20736365-DNA Primers,
pubmed-meshheading:20736365-Female,
pubmed-meshheading:20736365-Genetic Vectors,
pubmed-meshheading:20736365-Homeodomain Proteins,
pubmed-meshheading:20736365-Humans,
pubmed-meshheading:20736365-Lung Neoplasms,
pubmed-meshheading:20736365-MicroRNAs,
pubmed-meshheading:20736365-Neoplasm Invasiveness,
pubmed-meshheading:20736365-Neoplasm Metastasis,
pubmed-meshheading:20736365-RNA, Messenger
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pubmed:year |
2010
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pubmed:articleTitle |
Ratio of miR-196s to HOXC8 messenger RNA correlates with breast cancer cell migration and metastasis.
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pubmed:affiliation |
Departments of Biochemistry and Molecular Biology, Cellular Biology and Anatomy, and Cancer Center, Medical College of Georgia, Augusta, GA 30912, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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