mRNA expression profiles show differential regulatory effects of microRNAs between estrogen receptor-positive and estrogen receptor-negative breast cancer

被引:85
作者
Cheng, Chao [1 ]
Fu, Xuping [2 ]
Alves, Pedro [1 ]
Gerstein, Mark [1 ,3 ,4 ]
机构
[1] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06511 USA
[2] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Inst Genet, Shanghai 200433, Peoples R China
[3] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA
[4] Yale Univ, Dept Comp Sci, New Haven, CT 06511 USA
来源
GENOME BIOLOGY | 2009年 / 10卷 / 09期
关键词
ALPHA ER-ALPHA; GENE-EXPRESSION; TARGET RECOGNITION; DICER; REPRESSION; MIRNAS; GROWTH; CELLS; PREDICTION; APOPTOSIS;
D O I
10.1186/gb-2009-10-9-r90
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background: Recent studies have shown that the regulatory effect of microRNAs can be investigated by examining expression changes of their target genes. Given this, it is useful to define an overall metric of regulatory effect for a specific microRNA and see how this changes across different conditions. Results: Here, we define a regulatory effect score (RE-score) to measure the inhibitory effect of a microRNA in a sample, essentially the average difference in expression of its targets versus non-targets. Then we compare the RE-scores of various microRNAs between two breast cancer subtypes: estrogen receptor positive (ER+) and negative (ER-). We applied this approach to five microarray breast cancer datasets and found that the expression of target genes of most microRNAs was more repressed in ER- than ER+; that is, microRNAs appear to have higher RE-scores in ER- breast cancer. These results are robust to the microRNA target prediction method. To interpret these findings, we analyzed the level of microRNA expression in previous studies and found that higher microRNA expression was not always accompanied by higher inhibitory effects. However, several key microRNA processing genes, especially Ago2 and Dicer, were differentially expressed between ER- and ER+ breast cancer, which may explain the different regulatory effects of microRNAs in these two breast cancer subtypes. Conlusions: The RE-score is a promising indicator to measure microRNAs' inhibitory effects. Most microRNAs exhibit higher RE-scores in ER- than in ER+ samples, suggesting that they have stronger inhibitory effects in ER(-)breast cancers.
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页数:17
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