Journal Article

Computational analysis of microRNA profiles and their target genes suggests significant involvement in breast cancer antiestrogen resistance

Fuxiao Xin, Meng Li, Curt Balch, Michael Thomson, Meiyun Fan, Yunlong Liu, Scott M. Hammond, Sun Kim and Kenneth P. Nephew

in Bioinformatics

Volume 25, issue 4, pages 430-434
Published in print February 2009 | ISSN: 1367-4803
Published online December 2008 | e-ISSN: 1460-2059 | DOI: http://dx.doi.org/10.1093/bioinformatics/btn646
Computational analysis of microRNA profiles and their target genes suggests significant involvement in breast cancer antiestrogen resistance

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Motivation: Recent evidence shows significant involvement of microRNAs (miRNAs) in the initiation and progression of numerous cancers; however, the role of these in tumor drug resistance remains unknown.

Results: By comparing global miRNA and mRNA expression patterns, we examined the role of miRNAs in resistance to the ‘pure antiestrogen’ fulvestrant, using fulvestrant-resistant MCF7-FR cells and their drug-sensitive parental estrogen receptor (ER)-positive MCF7 cells. We identified 14 miRNAs downregulated in MCF7-FR cells and then used both TargetScan and PITA to predict potential target genes. We found a negative correlation between expression of these miRNAs and their predicted target mRNA transcripts. In genes regulated by multiple miRNAs or having multiple miRNA-targeting sites, an even stronger negative correlation was found. Pathway analyses predicted these miRNAs to regulate specific cancer-associated signal cascades. These results suggest a significant role for miRNA-regulated gene expression in the onset of breast cancer antiestrogen resistance, and an improved understanding of this phenomenon could lead to better therapies for this often fatal condition.

Contact: knephew@indiana.edu; sunkim2@indiana.edu

Supplementary information: Supplementary data are available at Bioinformatics online.

Journal Article.  3176 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology

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