Source:http://linkedlifedata.com/resource/pubmed/id/20848182
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2011-3-16
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pubmed:abstractText |
Expression of certain microRNA genes is regulated by DNA methylation, which in turn affects the activities of their downstream molecules. Our previous study showed that methylated let-7a-3 was associated with low IGF-II expression and favorable prognosis of ovarian cancer. The roles of let-7a-3 methylation in breast cancer and in regulation of IGF expression in the tumor are still unknown. Let-7a-3 methylation, IGF mRNAs, and peptides were analyzed in 348 breast cancer samples using quantitative methylation-specific PCR, qRT-PCR, and ELISA, respectively. The associations of let-7a-3 methylation with IGFs, disease features, and patient survivals were analyzed. In vitro experiments were performed using HeLa cells transfected with let-7a precursors to assess the effect of let-7a on IGF expression. Let-7a-3 methylation was detected frequently in breast cancer. An inverse correlation between let-7a-3 methylation and IGF expression was observed in breast cancer, which was similar to that seen in ovarian cancer. Our in vitro experiment showed that let-7a could increase IGF expression in cancer cells which had low endogenous let-7a. Let-7a-3 methylation was also found to be associated with high grade tumors and ER- or PR-negative cancer. However, let-7a-3 methylation was not associated with disease-free survival or overall survival of breast cancer patients. The study provides further evidence in support of the notion that epigenetic regulation of let-7a-3 may affect the actions of IGFs in cancer. Let-7a may up-regulate the expression of IGFs in cancer cells, which is different from its inhibitory effects on other oncogenes.
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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 |
Apr
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pubmed:issn |
1573-7217
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
126
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
687-94
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pubmed:meshHeading |
pubmed-meshheading:20848182-Adult,
pubmed-meshheading:20848182-Aged,
pubmed-meshheading:20848182-Aged, 80 and over,
pubmed-meshheading:20848182-Breast Neoplasms,
pubmed-meshheading:20848182-DNA Methylation,
pubmed-meshheading:20848182-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:20848182-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:20848182-HeLa Cells,
pubmed-meshheading:20848182-Humans,
pubmed-meshheading:20848182-MicroRNAs,
pubmed-meshheading:20848182-Middle Aged,
pubmed-meshheading:20848182-Prognosis,
pubmed-meshheading:20848182-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20848182-Somatomedins
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pubmed:year |
2011
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pubmed:articleTitle |
Let-7a regulation of insulin-like growth factors in breast cancer.
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pubmed:affiliation |
Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, 60 College Street, New Haven, CT 06520-8034, USA.
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pubmed:publicationType |
Journal Article
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