A conserved microRNA signature related to cellular transformation by the RAS oncogene (Affymetrix mRNA)

The differential expression of microRNAs in Ras transformed epithelial cells of human and rat origin was investigated. Here we describe the group of miRNAs differentially expressed in two Ras transformed cell lines and defined it as a miRNA Ras signatures. We show that expression of these miRNAs are also affected in different primary tumors with high frequency of Ras mutation. We demonstate that introduction of different miRNAs lost during Ras transformation have big influence on cellular phenotype and mRNA expression. Importance of Ras pathway dependent transcription factors for miRNA regulation was shown as well. The complexity of miRNA – signal transduction pathways interactions and importance of miRNA regulation in Ras dependent malignant tumor formation is discussed.本研究针对人源及大鼠源的Ras转化上皮细胞中的微小核糖核酸（microRNA，简称miRNA）差异表达情况展开了系统探究。本研究鉴定出在两种Ras转化细胞系中存在差异表达的miRNA集合，并将其定义为miRNA Ras特征（miRNA Ras signatures）。研究证实，上述miRNA的表达在Ras突变频率较高的各类原发性肿瘤中同样存在异常改变。本研究证明，恢复在Ras转化过程中缺失的不同miRNA的表达，可对细胞表型及信使核糖核酸（mRNA）的表达产生显著影响。此外，本研究还验证了依赖Ras通路的转录因子在miRNA调控中的关键作用，并探讨了miRNA与信号转导通路之间相互作用的复杂性，以及miRNA调控在Ras依赖性恶性肿瘤发生过程中的重要意义。