let-7-regulated oncogenic mRNAs

let-7-regulated oncogenic mRNAs refers to a group of transcripts that are post-transcriptionally repressed by the let-7 microRNA family, which acts as a master tumor suppressor (Johnson et al., 2005, Cell). These mRNAs are characterized by the presence of one or more "seed-matched" binding sites in their 3' untranslated regions (3'UTRs), specifically complementary to the 5' end of the let-7 microRNA (Mayr et al., 2007, Science). Key members of this group include potent oncogenes such as KRAS, MYC, and HMGA2, which drive cell proliferation, survival, and epithelial-mesenchymal transition (Sampson et al., 2007, Cancer Res). In many cancers, the downregulation of let-7 or the loss of these binding sites (e.g., through 3'UTR shortening) leads to the overexpression of these oncogenic proteins, contributing to tumor progression and poor prognosis (Bussing et al., 2008, Trends Mol Med). Therapeutic strategies targeting this axis include the use of synthetic let-7 mimics to restore regulation or small molecules that inhibit the LIN28 protein, a negative regulator of let-7 biogenesis. Additionally, direct inhibitors of the proteins encoded by these mRNAs, such as KRAS G12C inhibitors, are used to counteract the effects of let-7 loss. The complexity of the let-7 regulatory network makes these mRNAs significant targets for both diagnostic and therapeutic intervention in oncology.

Other names

let-7 targetslet-7 seed-matched mRNAslet-7 regulated geneslet-7 responsive oncogenes

MicroRNA-mediated gene silencing via translational repression and mRNA degradation.