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The Kruppel-like factor 12 (KLF12) mRNA 3′ untranslated region (3′UTR) is a regulatory sequence located immediately downstream of the KLF12 coding region, playing a pivotal role in the post-transcriptional control of KLF12 expression (UniProt Q9Y4X4). KLF12 itself is a zinc-finger transcription factor that typically acts as a repressor, influencing biological processes such as the cell cycle, lung development, and various oncogenic pathways (PubMed: 29328357). The 3′UTR serves as a primary docking site for microRNAs (miRNAs), including miR-141, miR-20b, and miR-137, which bind to specific seed sequences to induce mRNA degradation or inhibit translation (PubMed: 32154012, PubMed: 30603484). In the context of oncology, the interaction between these miRNAs and the KLF12 3′UTR is frequently disrupted, leading to the overexpression of KLF12 and subsequent promotion of tumor cell proliferation and metastasis in gastric, colorectal, and lung cancers (PubMed: 29328357). As a result, this region is considered a significant target for RNA-based therapeutics, such as miRNA mimics or antisense oligonucleotides, aimed at restoring regulatory control over KLF12 (PubMed: 32154012). Therapeutic development focusing on this target faces challenges common to RNA-targeted drugs, including the need for efficient delivery systems and the mitigation of off-target effects (PubMed: 30603484). Understanding the structural and sequence-specific interactions within this 3′UTR is essential for developing precise interventions that can restore normal cellular homeostasis in KLF12-associated diseases.
MicroRNA-mediated gene silencing through sequence-specific binding to the 3′UTR, leading to mRNA degradation or translational repression of the KLF12 transcript (PubMed: 29328357, PubMed: 32154012).
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