Oncogenic mRNA targets of let-7 (let-7 targets) (let-7 targets)

The let-7 (lethal-7) microRNA family functions as a critical tumor suppressor by post-transcriptionally regulating a network of oncogenic mRNAs (Johnson et al., 2005, Cell). Key targets include major drivers of human malignancy such as KRAS, MYC, and HMGA2, which are often overexpressed in various cancers due to the loss of let-7 (Sampson et al., 2007, Cancer Research; Mayr et al., 2007, Science). By binding to the 3' untranslated regions (UTRs) of these mRNAs, let-7 induces translational repression and mRNA degradation, thereby inhibiting cell proliferation, survival, and the epithelial-mesenchymal transition (Boyerinas et al., 2010, Cancer Research). Therapeutic intervention typically involves the delivery of synthetic let-7 mimics to restore this natural regulatory mechanism and simultaneously silence multiple oncogenic pathways. However, challenges remain regarding the efficient delivery of these RNA-based therapeutics and the potential for off-target effects or immune stimulation (Rupaimoole & Slack, 2017, Nature Reviews Drug Discovery). Restoration of let-7 has shown promise in preclinical models of lung, breast, and liver cancers by effectively reducing the expression of its oncogenic targets. The complexity of the let-7 targetome necessitates careful consideration of the systemic effects of global mRNA suppression.

Other names

let-7 regulated oncogeneslet-7 downstream targetsLethal-7 targetslet-7 targetome

miRNA-mediated gene silencing via binding to the 3' untranslated region (UTR) of target mRNAs, leading to translational repression and mRNA degradation.