MicroRNAs Regulate Expression of Oncogenes

Featured Article: Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, et al. RAS is regulated by the let-7 microRNA family. Cell 2005;120:635–47.2Today, we fully appreciate that microRNAs (miRNAs)3 represent a paradigm shift in our understanding of gene expression and disease, but it was not always this way. miRNAs are small noncoding RNAs belonging to a novel class of regulatory molecules in plants and animals that control the expression of hundreds of target mRNA transcripts. Thousands of known miRNAs regulate gene expression by binding to imperfect complementary sites within the 3′ untranslated regions (UTRs) of their target protein–coding mRNAs and repressing the expression of these genes at the level of mRNA stability and translation (1). Recent progress has revealed that miRNAs are involved in the regulation of most biological functions, including development, life span, and metabolism, and their dysregulation contributes, not surprisingly, to many types of disease, notably cancer (2). For example, certain miRNAs regulate processes important for cell growth, division, differentiation, survival, and migration—all processes that go awry in cancer. In addition, several key miRNA genes known to be amplified, deleted, or misexpressed in cancer (3) act in …