Lethal-7 family microRNA (let-7)

The let-7 (lethal-7) family of microRNAs is one of the most extensively studied and evolutionarily conserved groups of non-coding RNAs, originally discovered in C. elegans as a regulator of developmental timing. In humans, the family consists of multiple members (e.g., let-7a-i, miR-98) that primarily function as tumor suppressors by post-transcriptionally repressing key oncogenes such as RAS, MYC, and HMGA2. Beyond cancer, let-7 microRNAs play critical roles in cell differentiation, stem cell maintenance, metabolism, and immune response regulation. Their downregulation is a hallmark of many cancers and is often associated with poor prognosis and the maintenance of cancer stem cells. Therapeutic strategies targeting the let-7 pathway include the use of synthetic let-7 mimics to restore tumor-suppressive function and small-molecule inhibitors of Lin28, a protein that normally blocks let-7 biogenesis. Despite their therapeutic potential, challenges such as efficient delivery to target tissues and the risk of off-target effects remain significant hurdles in the development of let-7-based medicines.

Other names

let-7 familyLethal-7MIRLET7miR-let-7let-7 microRNA

RNA interference (RNAi) leading to translational repression and mRNA degradation of target oncogenes (e.g., RAS, MYC, HMGA2) by binding to their 3' untranslated regions (3' UTRs).