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The let-7 microRNA Family Regulates RAS: Implications for Development and Oncogenesis

Research Summary
Drs. Frank Slack, Steven Johnson, and Helge Grosshans, and Ms. Kristy Reinert at Yale University, in collaboration with Ambion scientists, discovered that the let-7 microRNA (miRNA) family regulates the expression of let-60/RAS in C. elegans epidermal and vulval cells, and this work was extended to humans. As detailed in the March issue of Cell [1], let-7 miRNAs regulate human RAS oncogene expression and are often down-regulated in human lung tumors. The correlation between let-7 miRNA reduction and RAS protein induction in human lung cancer suggests that misregulation of let-7 miRNA might contribute to oncogenesis by enabling significant up-regulation of RAS protein expression.


let-7 miRNAs Regulate let-60/RAS in C. elegans During Development

The epidermis in C. elegans is made of three main cell types: seam, syncytial, and P cells. Temporal up-regulation of let-7 miRNA in the seam cells [23] is required for terminal differentiation at the adult stage [3], which is when these cells exit the cell cycle, fuse together, and excrete cuticular alae (the longitudinal external ridges on the sides of each animal) [4]. To understand how the let-7 gene family affects cell differentiation, Dr. Frank Slack and his colleagues used a computational approach to identify eleven development genes that
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