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The MicroRNA-17 (miR-17) binding element is a highly conserved regulatory nucleotide sequence typically located within the 3' untranslated region (UTR) of various messenger RNAs (mRNAs) [15, 20]. This element serves as the primary recognition site for the miR-17 family of microRNAs, which, upon binding, recruits the RNA-induced silencing complex (RISC) to suppress gene expression through mRNA degradation or translational inhibition [3, 13, 22]. In diseases such as Autosomal Dominant Polycystic Kidney Disease (ADPKD), miR-17 is pathologically upregulated and binds to these elements on PKD1 and PKD2 transcripts, leading to the repression of Polycystin proteins and subsequent cyst formation [1, 5]. In oncology, miR-17 binding elements in tumor suppressor genes like PTEN and E2F1 are often exploited by overexpressed 'oncomiRs' to drive cell proliferation and survival [19, 21]. Therapeutic strategies involving this target include anti-miR oligonucleotides, such as RGLS4326 and RGLS8429, which sequester the microRNA to prevent its interaction with the binding element, as well as experimental target site blockers (TSBs) that specifically mask the sequence on the mRNA to restore homeostatic gene expression [2, 7, 10, 11].
Competitive inhibition of microRNA binding, steric hindrance of the RNA-induced silencing complex (RISC), and de-repression of target messenger RNA (mRNA) to restore protein translation.
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