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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-3-16
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1573-7217
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
126
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
687-94
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Let-7a regulation of insulin-like growth factors in breast cancer.
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.
pubmed:publicationType
Journal Article