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The Yes-associated protein 1 (YAP1) mRNA 3' untranslated region (3' UTR) is a critical regulatory segment of the YAP1 transcript that governs the stability, localization, and translation efficiency of the YAP1 protein [1, 11]. As a central effector of the Hippo signaling pathway, YAP1 plays a pivotal role in organ size control, cell proliferation, and stem cell maintenance [10, 14]. The 3' UTR contains numerous binding sites for microRNAs (miRNAs) and RNA-binding proteins, such as hnRNP F, which can induce alternative splicing or degradation of the mRNA to modulate YAP1 levels [3, 7]. Dysregulation of YAP1, often through the loss of these inhibitory controls in the 3' UTR, is a hallmark of various cancers, including hepatocellular carcinoma and lung cancer, where it drives tumor progression and chemoresistance [6, 12, 17]. Consequently, the YAP1 mRNA 3' UTR has emerged as a therapeutic target for antisense oligonucleotides (ASOs) and RNA-based therapies designed to reduce oncogenic YAP1 expression [2, 9]. For example, the ASO ION-537 is designed to bind specifically to the YAP1 transcript to induce its degradation, thereby reducing the levels of this potent oncogene in tumors [9].
Antisense inhibition, RNA interference (RNAi), miRNA-mediated silencing, mRNA degradation, Splicing modulation
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