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

School of Informatics, Indiana University, Bloomington, IN 47405, USA.
Bioinformatics (Impact Factor: 4.62). 01/2009; 25(4):430-4. DOI: 10.1093/bioinformatics/btn646
Source: PubMed

ABSTRACT 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.

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    ABSTRACT: MicroRNAs (miRNAs) are small non-coding RNAs generated by a two-step complex process and are post transcriptional negative regulators of their target mRNAs. Dysregulation of many of these miRNAs has been associated with tumorigenesis in various cancers including breast cancer. Aberrantly high expression of specific miRNAs in breast cancer cells is demonstrated to be linked with inhibition of tumor suppressor genes and promote tumorigenesis. They are classified as oncogenic miRNAs. However, the tumor suppressor miRNAs are downregulated in breast cancer cells, since their major targets are oncogenic mRNAs. Understanding mechanism of action of specific miRNAs in breast cancer cells can be utilized to develop newer anti-cancer therapies. Recently, newer techniques are also developed to detect abundance of specific miRNA in the blood plasma samples and can be used in early diagnosis or prognosis in breast cancer. In this review article, we have discussed several miRNAs dysregulated in breast cancer and their therapeutic potential.
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