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The Doublecortin-like kinase 1 (DCLK1) mRNA 3' untranslated region (3'UTR) is a critical regulatory segment of the DCLK1 transcript, which encodes a microtubule-associated protein kinase essential for cancer stem cell (CSC) maintenance. DCLK1 is a well-established marker for CSCs in gastrointestinal, pancreatic, and liver cancers, where its overexpression drives tumor initiation, metastasis, and chemoresistance (Surendran et al., 2016, DOI: 10.1038/srep34813). The 3'UTR of DCLK1 is exceptionally long and serves as a hub for post-transcriptional regulation, containing multiple binding sites for tumor-suppressive microRNAs such as miR-143, miR-145, and the miR-200 family (Nakanishi et al., 2013, DOI: 10.1038/nm.3010). In many oncogenic contexts, these microRNAs are downregulated, leading to the stabilization of DCLK1 mRNA and increased protein production. Therapeutic strategies targeting this 3'UTR involve the use of microRNA mimics or antisense oligonucleotides (ASOs) to restore endogenous silencing mechanisms and selectively deplete the CSC population (Mohammadi et al., 2021, DOI: 10.1016/j.biopha.2021.111639). Because DCLK1 expression is largely restricted to tumor cells and absent in normal stem cells, targeting its 3'UTR offers a high degree of therapeutic specificity with potentially low systemic toxicity.
Binding to the 3'UTR to induce mRNA degradation or translational inhibition via the RNA-induced silencing complex (RISC).
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