title: Computational analysis of microRNA profiles and their target genes suggests significant involvement in breast cancer antiestrogen resistance.
abstract: BACKGROUND
  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.affiliation: School of Informatics, Indiana University, Bloomington, IN 47405, USA.
authors.forename: Fuxiao
authors.initials: F
authors.lastname: Xin
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.forename: Curt
authors.initials: C
authors.lastname: Balch
authors.forename: Michael
authors.initials: M
authors.lastname: Thomson
authors.forename: Meiyun
authors.initials: M
authors.lastname: Fan
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Liu
authors.forename: Scott M
authors.initials: SM
authors.lastname: Hammond
authors.forename: Sun
authors.initials: S
authors.lastname: Kim
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Nephew
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D045744:Cell Line, Tumor; D019295:Computational Biology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*
chemical_list: D020847:Estrogen Receptor Modulators; D035683:MicroRNAs