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The IQ motif containing GTPase activating protein 1 (IQGAP1) mRNA 3′-untranslated region (3′-UTR) miR-124a binding site is a specific regulatory sequence that serves as a target for microRNA-124a (miR-124a), a brain-enriched microRNA with tumor-suppressive properties (Sun et al., 2014, PLoS ONE). Binding of miR-124a to this site facilitates the recruitment of the RNA-induced silencing complex (RISC), resulting in the post-transcriptional downregulation of IQGAP1 through mRNA degradation or translational repression (Chen et al., 2014, International Journal of Oncology). IQGAP1 itself is a scaffold protein that integrates multiple signaling pathways, including those involving Rho GTPases and the MAPK/ERK cascade, to regulate cytoskeletal dynamics and cell-cell adhesion (Wang et al., 2018, Oncology Reports). In various malignancies such as glioma, hepatocellular carcinoma, and gastric cancer, miR-124a is frequently downregulated, leading to the pathological overexpression of IQGAP1 and subsequent promotion of tumor cell proliferation and metastasis (Sun et al., 2014, PLoS ONE). This binding site is therefore a critical node for therapeutic intervention, where miR-124 mimics or antisense oligonucleotides can be employed to modulate IQGAP1 levels and inhibit oncogenic signaling. However, the therapeutic application of miR-124a mimics is complicated by the microRNA's ability to target multiple other genes, potentially leading to significant off-target effects (Chen et al., 2014, International Journal of Oncology).
MicroRNA-mediated gene silencing via the RNA-induced silencing complex (RISC), leading to mRNA cleavage or translational inhibition of the IQGAP1 transcript (Sun et al., 2014, PLoS ONE).
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