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The Proliferating cell nuclear antigen (PCNA) messenger RNA 3' untranslated region (3'UTR) is a critical regulatory segment of the PCNA transcript that governs mRNA stability and translation efficiency (PubMed: 10854306). PCNA itself functions as a DNA clamp and a processivity factor for DNA polymerase delta, making it indispensable for DNA replication and various DNA repair pathways (UniProt: P12004). In many cancers, PCNA is significantly overexpressed to support rapid cell proliferation, making its mRNA a viable therapeutic target (PubMed: 25635393). Antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) designed to bind the PCNA mRNA 3'UTR can trigger the degradation of the transcript or physically block the translation machinery (PubMed: 15103328). This reduction in PCNA protein levels disrupts the replication fork and induces cell cycle arrest and apoptosis in malignant cells. While targeting the 3'UTR offers a strategy to downregulate this essential protein, challenges include ensuring tumor-specific delivery and minimizing effects on healthy, rapidly dividing cells (PubMed: 19029616).
Antisense-mediated mRNA degradation (RNase H-dependent) or translational inhibition, leading to reduced PCNA protein expression and subsequent inhibition of DNA replication and repair.
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