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The Caspase-9 (CASP9) mRNA 3' untranslated region (3'UTR) is a critical regulatory segment of the CASP9 transcript that governs the expression of the initiator caspase of the intrinsic apoptotic pathway (UniProt P55210). This region contains multiple binding sites for microRNAs (miRNAs) and RNA-binding proteins that influence mRNA stability and translation efficiency. In many cancers, overexpression of specific miRNAs, such as miR-24-3p or miR-23a, targeting the CASP9 3'UTR leads to the downregulation of Caspase-9 protein, allowing cells to evade programmed cell death (Xie et al., 2013; Yong et al., 2014). Consequently, the CASP9 mRNA 3'UTR has emerged as a potential therapeutic target for RNA-based interventions, such as antisense oligonucleotides (ASOs) or miRNA inhibitors, designed to restore Caspase-9 levels and sensitize tumor cells to apoptosis. Beyond oncology, dysregulation of this region may play a role in neurodegenerative conditions where aberrant apoptosis occurs. Targeting this RNA structure requires precise delivery and sequence specificity to avoid off-target effects and systemic toxicity.
Modulation of mRNA stability and translation efficiency by blocking or mimicking the binding of microRNAs and RNA-binding proteins to the 3' untranslated region (Xie et al., 2013).
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