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.
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.
Authors: Kyle Kai-How Farh; Andrew Grimson; Calvin Jan; Benjamin P Lewis; Wendy K Johnston; Lee P Lim; Christopher B Burge; David P Bartel Journal: Science Date: 2005-11-24 Impact factor: 47.728
Authors: Hua Yang; William Kong; Lili He; Jian-Jun Zhao; Joshua D O'Donnell; Jiawang Wang; Robert M Wenham; Domenico Coppola; Patricia A Kruk; Santo V Nicosia; Jin Q Cheng Journal: Cancer Res Date: 2008-01-15 Impact factor: 12.701
Authors: Paul E Blower; Ji-Hyun Chung; Joseph S Verducci; Shili Lin; Jong-Kook Park; Zunyan Dai; Chang-Gong Liu; Thomas D Schmittgen; William C Reinhold; Carlo M Croce; John N Weinstein; Wolfgang Sadee Journal: Mol Cancer Ther Date: 2008-01-09 Impact factor: 6.261
Authors: Kelly H Salter; Chaitanya R Acharya; Kelli S Walters; Richard Redman; Ariel Anguiano; Katherine S Garman; Carey K Anders; Sayan Mukherjee; Holly K Dressman; William T Barry; Kelly P Marcom; John Olson; Joseph R Nevins; Anil Potti Journal: PLoS One Date: 2008-04-02 Impact factor: 3.240
Authors: Tissa T Manavalan; Yun Teng; Savitri N Appana; Susmita Datta; Theodore S Kalbfleisch; Yong Li; Carolyn M Klinge Journal: Cancer Lett Date: 2011-09-10 Impact factor: 8.679