Landscape of microRNA regulatory network architecture and functional rerouting in cancer

摘要: Somatic mutations are a major source of cancer development, and many driver mutations have been identified in protein coding regions. However, the function of mutations located in miRNA and their target binding sites throughout the human genome remains largely unknown. Here, we built detailed cancer-specific miRNA regulatory networks across 30 cancer types to systematically analyze the effect of mutations in miRNAs and their target sites in 3′ untranslated region (3′ UTR), coding sequence (CDS), and 5′ UTR regions. A total of 3,518,261 mutations from 9,819 samples were mapped to miRNA–gene interactions (mGI). Mutations in miRNAs showed a mutually exclusive pattern with mutations in their target genes in almost all cancer types. A linear regression method identified 148 candidate driver mutations that can significantly perturb miRNA regulatory networks. Driver mutations in 3 …