Xin Fuxiao, Li Meng, Balch Curt, Thomson Michael, Fan Meiyun, Liu Yunlong, Hammond Scott M, Kim Sun, Nephew Kenneth P
School of Informatics, Indiana University, Bloomington, IN 47405, USA.
Bioinformatics. 2009 Feb 15;25(4):430-4. doi: 10.1093/bioinformatics/btn646. Epub 2008 Dec 17.
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.
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.
近期证据表明，微小RNA（miRNA）在多种癌症的发生和发展中发挥着重要作用；然而，它们在肿瘤耐药性中的作用仍不清楚。
通过比较整体miRNA和mRNA表达模式，我们利用氟维司群耐药的MCF7-FR细胞及其药物敏感的亲代雌激素受体（ER）阳性MCF7细胞，研究了miRNA在对“纯抗雌激素药物”氟维司群耐药中的作用。我们鉴定出14种在MCF7-FR细胞中表达下调的miRNA，然后使用TargetScan和PITA预测潜在的靶基因。我们发现这些miRNA的表达与其预测的靶mRNA转录本之间呈负相关。在受多个miRNA调控或具有多个miRNA靶向位点的基因中，发现了更强的负相关。通路分析预测这些miRNA可调节特定的癌症相关信号级联反应。这些结果表明，miRNA调控的基因表达在乳腺癌抗雌激素耐药的发生中起重要作用，更好地理解这一现象可能会为这种常致命的疾病带来更好的治疗方法。
