Dataset Information

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

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.

SUBMITTER: Xin F

PROVIDER: S-EPMC2642642 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Xin Fuxiao F Li Meng M Balch Curt C Thomson Michael M Fan Meiyun M Liu Yunlong Y Hammond Scott M SM Kim Sun S Nephew Kenneth P KP

Bioinformatics (Oxford, England) 20081217 4

<h4>Motivation</h4>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.<h4>Results</h4>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 ...[more]

PMID: 19091772

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Project description:MicroRNAs (miRNAs) are small ~22 nucleotide non-coding RNAs that function as post-transcriptional regulators of messenger RNA (mRNA) through base-pairing to 6-8 nucleotide long target sites, usually located within the mRNA 3' untranslated region. A common approach to validate and probe microRNA-mRNA interactions is to mutate predicted target sites within the mRNA and determine whether it affects miRNA-mediated activity. The introduction of miRNA target site mutations, however, is potentially problematic as it may generate new, "illegitimate sites" target sites for other miRNAs, which may affect the experimental outcome. While it is possible to manually generate and check single miRNA target site mutations, this process can be time consuming, and becomes particularly onerous and error prone when multiple sites are to be mutated simultaneously. We have developed a modular Java-based system called ImiRP (Illegitimate miRNA Predictor) to solve this problem and to facilitate miRNA target site mutagenesis.The ImiRP interface allows users to input a sequence of interest, specify the locations of multiple predicted target sites to mutate, and set parameters such as species, mutation strategy, and disallowed illegitimate target site types. As mutant sequences are generated, ImiRP utilizes the miRBase high confidence miRNA dataset to identify illegitimate target sites in each mutant sequence by comparing target site predictions between input and mutant sequences. ImiRP then assembles a final mutant sequence in which all specified target sites have been mutated.ImiRP is a mutation generator program that enables selective disruption of specified miRNA target sites while ensuring predicted target sites for other miRNAs are not inadvertently created. ImiRP supports mutagenesis of single and multiple miRNA target sites within a given sequence, including sites that overlap. This software will be particularly useful for studies looking at microRNA cooperativity, where mutagenesis of multiple microRNA target sites may be desired. The software is available at imirp.org and is available open source for download through GitHub ( https://github.com/imirp ).

Dataset Information

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

Motivation

Results

Publications

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

Similar Datasets

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