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Pre-let-7f is a precursor microRNA (pre-miRNA) that serves as the intermediate in the biogenesis of mature let-7f, a key member of the highly conserved lethal-7 (let-7) microRNA family (Wikipedia, 2024). It is characterized by a hairpin-loop structure that is recognized and cleaved by the Dicer enzyme in the cytoplasm to produce the functional 22-nucleotide mature miRNA (NIH, 2024). Let-7f functions as a potent tumor suppressor by binding to the 3-untranslated regions (UTRs) of various oncogenic mRNAs, including RAS, MYC, and HMGA2, thereby inhibiting their translation or promoting their degradation (NIH, 2024; MDPI, 2021). In many human cancers, the biogenesis of let-7f is actively suppressed by the RNA-binding proteins Lin28A and Lin28B, which bind to the terminal loop of pre-let-7f and recruit terminal uridylyltransferases (TUTases) to induce its degradation (NIH, 2024; Molecular Cell, 2008). This Lin28/let-7 axis is a significant therapeutic target, with drug development efforts focusing on small-molecule inhibitors that disrupt the Lin28-pre-miRNA interaction to restore tumor-suppressive let-7 levels (NIH, 2024; Grantome, 2024). Additionally, synthetic let-7 mimics are being explored as replacement therapies to bypass the biogenesis blockade and suppress tumor growth and metastasis (NIH, 2024).
Restoration of tumor suppressor function; Inhibition of miRNA biogenesis; Prevention of Lin28-mediated degradation and uridylation
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