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The Aryl hydrocarbon receptor (AHR) mRNA 3' untranslated region (UTR) is a critical regulatory segment of the AHR transcript that governs the stability and translation efficiency of the receptor protein (UniProt P35869). As a ligand-activated transcription factor, AHR plays a pivotal role in xenobiotic metabolism, immune response modulation, and cellular proliferation. The 3' UTR contains specific binding sites for various microRNAs (miRNAs), such as miR-124 and miR-203, which act as endogenous negative regulators to suppress AHR expression (Zhao et al., 2016, Oncotarget; Huang et al., 2015, Journal of Biological Chemistry). Dysregulation of AHR expression, often mediated by alterations in its 3' UTR interactions or miRNA availability, is linked to various cancers where it can promote tumor progression, epithelial-mesenchymal transition, and immune evasion (Safe et al., 2013, Toxicological Sciences). Consequently, the AHR mRNA 3' UTR has emerged as a potential therapeutic target for RNA-based interventions, such as miRNA mimics or antisense oligonucleotides, aimed at modulating AHR levels in diseases like glioblastoma and other solid tumors. Targeting this region allows for the precise down-regulation of AHR protein production, offering a strategy to inhibit its pro-oncogenic signaling pathways.
MicroRNA-mediated gene silencing and antisense-mediated mRNA degradation or translational inhibition
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