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The YES1 mRNA 3' untranslated region (3'UTR) is a critical regulatory segment of the messenger RNA encoding the YES1 protein, a member of the Src family of non-receptor tyrosine kinases (UniProt P07947). This region contains multiple binding sites for microRNAs and RNA-binding proteins that dictate the stability and translation efficiency of the YES1 transcript (PubMed: 28438057). In many cancers, including non-small cell lung cancer and esophageal carcinoma, YES1 is overexpressed and acts as a driver of proliferation, survival, and resistance to tyrosine kinase inhibitors (PubMed: 25212601). Targeting the 3'UTR specifically allows for the modulation of YES1 protein levels at the post-transcriptional level, offering a strategy to overcome resistance in tumors where the protein itself is difficult to inhibit directly (PubMed: 32663398). Therapeutic approaches include the use of antisense oligonucleotides (ASOs) and small molecules designed to bind specific secondary structures within the 3'UTR, often leading to mRNA degradation or translational blockade (PubMed: 32663398). These RNA-targeted strategies represent a novel frontier in precision oncology, aiming to silence oncogenic drivers that were previously considered undruggable at the protein level.
Targeted mRNA degradation via RNase L recruitment or RNase H-mediated cleavage, and translational inhibition.
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