1. RAS Is Regulated by the let-7 MicroRNA Family
- Author
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Steven M. Johnson, Emmanuel Labourier, Jaclyn Shingara, David Brown, Rich Jarvis, Angie Cheng, Kristy L. Reinert, Helge Grosshans, Mike Byrom, and Frank J. Slack
- Subjects
Lung Neoplasms ,Cellular differentiation ,Molecular Sequence Data ,Cell ,Down-Regulation ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Genes, Reporter ,microRNA ,medicine ,Animals ,Humans ,Cell Lineage ,Caenorhabditis elegans ,Caenorhabditis elegans Proteins ,3' Untranslated Regions ,Gene ,Regulation of gene expression ,Reporter gene ,Biochemistry, Genetics and Molecular Biology(all) ,Three prime untranslated region ,Carcinoma ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Molecular biology ,Phenotype ,Cell biology ,MicroRNAs ,Cell Transformation, Neoplastic ,medicine.anatomical_structure ,ras Proteins ,HeLa Cells - Abstract
SummaryMicroRNAs (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° 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.
- Published
- 2005
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