Oncogenic messenger RNAs with canonical let-7c seed sites

Oncogenic messenger RNAs (mRNAs) with canonical let-7c seed sites represent a diverse group of transcripts post-transcriptionally regulated by the tumor-suppressive microRNA let-7c (Roush & Slack, 2008, Trends Cell Biol). The let-7 family is highly conserved and plays a critical role in regulating cell proliferation and differentiation by targeting potent oncogenes (Bussing et al., 2008, Mol Cell). These mRNAs contain specific sequences in their 3' untranslated regions (UTRs) that are complementary to the let-7c seed region, typically nucleotides 2-7, which facilitates RNA-induced silencing complex (RISC) binding. Binding of let-7c to these sites leads to the degradation of the mRNA or the inhibition of its translation into protein, thereby reducing oncogenic signaling. Key targets include members of the RAS family (Johnson et al., 2005, Cell), MYC (Sampson et al., 2007, Cancer Res), and HMGA2 (Lee & Dutta, 2007, Genes Dev). In various human malignancies, let-7c is frequently downregulated, contributing to tumor growth, metastasis, and poor prognosis. Therapeutic strategies focus on miRNA replacement therapy, using synthetic let-7c mimics to restore the natural suppression of these oncogenes. However, this approach faces significant challenges, including the efficient delivery of RNA molecules to target tissues and the potential for off-target effects across the transcriptome.

Other names

let-7c target mRNAslet-7c-regulated oncogeneslet-7c-responsive transcripts

MicroRNA-mediated gene silencing via mRNA degradation or translational inhibition through binding to complementary seed sites in the 3' untranslated region (UTR).