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MicroRNA 16 (miR-16) is a critical tumor-suppressive microRNA belonging to the miR-15/16 cluster, which is frequently deleted or downregulated in various malignancies, most notably B-cell chronic lymphocytic leukemia (CLL) (Calin et al., 2002, Proc Natl Acad Sci U S A). It functions by binding to the 3' untranslated regions (UTRs) of multiple oncogenic mRNAs, leading to their degradation or translational inhibition. Key validated targets include the anti-apoptotic protein BCL2 and cell cycle regulators such as Cyclin D1 (CCND1) and CDK6 (Cimmino et al., 2005, Proc Natl Acad Sci U S A; Liu et al., 2008, Nucleic Acids Res). By suppressing these targets, miR-16 induces apoptosis and arrests the cell cycle at the G1 phase. In therapeutic development, miR-16 mimics like TargomiRs have been tested in clinical trials for patients with malignant pleural mesothelioma, demonstrating the feasibility of miRNA-based replacement therapy (van Zandwijk et al., 2017, Lancet Oncol). Challenges include ensuring targeted delivery and minimizing off-target effects associated with the broad regulatory network of microRNAs.
Agonism of the miR-16 pathway via synthetic miRNA mimics to induce RNA interference-mediated silencing of oncogenic targets such as BCL2 and CCND1.
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