Johnson, SM; Grosshans, H; Shingara, J; Byrom, M; Jarvis, R; Cheng, A; Labourier, E; Reinert, KL; Brown, D; Slack, FJ Cell 2005,120(5)635-647 引用次数 1039
这篇发表于2005年的Cell杂志的文章报道了重要的miRNA家族——let-7 family负调控Ras基因表达及其机制，let-7家族miRNA水平在肺癌等Ras高表达的肿瘤中显著下调。
【摘要】MicroRNAs (miRNAs) are regulatory RNAs found in multicellular eukaryotes, including humans, where they are implicated in cancer. The let-7 miRNA times seam cell terminal differentiation in C. elegans. Here we show that the let-7 family negatively regulates let-60/RAS. Loss of let-60/RAS suppresses let-7, and the let-60/RAS 3'UTR contains multiple let-7 complementary sites (LCSs), restricting reporter gene expression in a let-7-dependent manner. mir-84, a let-7 family member, is largely absent in vulval precursor cell P6.p at the time that let-60/RAS specifies the 1 degrees vulval fate in that cell, and mir-84 overexpression suppresses the multivulva phenotype of activating let-60/ RAS mutations. The 3'UTRs of the human RAS genes contain multiple LCSs, allowing let-7 to regulate RAS expression. let-7 expression is lower in lung tumors than in normal lung tissue, while RAS protein is significantly higher in lung tumors, providing a possible mechanism for let-7 in cancer.
