{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMIR452 exhibits versatile, context‐dependent functions in human malignancies. In urothelial carcinoma, for example, it is overexpressed in node‐positive tumors and serves as an excellent prognostic marker for disease‐specific death."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In melanoma, the miR‐224/452 cluster is activated by E2F1 to promote epithelial–mesenchymal transition (EMT) and invasive behavior"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", whereas in lung adenocarcinoma and T‐cell acute lymphoblastic leukemia, reduced MIR452 levels are associated with increased tumor progression and a loss of cell growth control."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In colorectal and gastric cancers, elevated MIR452 not only promotes cell proliferation and migration by engaging oncogenic signalling such as Wnt/β‐catenin but also downregulates key tumor suppressors including GTF2E1 and EPB41L3."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctional studies further reveal that MIR452 modulates therapeutic response and the maintenance of cancer stem-like properties. In hepatocellular carcinoma, its upregulation enhances cell cycle progression and stemness by targeting regulators such as CDKN1B, Sox7, and CPEB3, thereby impacting pathways like Wnt/β‐catenin signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "12"}]}, {"type": "t", "text": " In breast cancer, differential expression of MIR452 is linked to chemoresistance: its altered levels influence the response to docetaxel and adriamycin, in part through regulation of targets such as IGF-1R and APC4."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "15"}]}, {"type": "t", "text": " Moreover, in epithelial ovarian cancer, NF-κB–driven MIR452-5p expression sustains tumor-initiating cell properties."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in oncogenesis, MIR452 participates in diverse nonmalignant processes. In adipocytes, intermittent hypoxia leads to its downregulation, which in turn elevates pro-inflammatory adipokines such as RETN, TNFα, and CCL2, thereby contributing to insulin resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": " MIR452 also exerts antiviral activity by binding to the VP3 region of Enterovirus 71 to repress viral replication"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": ", and it modulates STAT3 expression in models of noise-induced hearing loss."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRegulatory networks further refine MIR452 function across different biological systems. In immune-related contexts, aberrant MIR452 expression is observed in thymic hyperplasia associated with myasthenia gravis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": " In prostate and nasopharyngeal carcinomas, long noncoding RNAs such as SOX2-OT and LINC01140 act as molecular sponges for MIR452-5p, thereby modulating downstream effectors like HMGB3 and ZNF621 to influence cell proliferation and radiosensitivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": " In gastric cancer, the circRNA circKIAA0907 sequesters MIR452-5p to upregulate the tumor suppressor KAT6B and thereby curb tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": " Moreover, MIR452 is implicated in colorectal inflammation and colitis through regulation of the IL20RA/JAK–STAT axis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}, {"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "25"}]}, {"type": "t", "text": ", and emerging roles in airway remodeling have been suggested in models of goblet cell metaplasia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "26"}]}, {"type": "t", "text": " Comprehensive reviews emphasize the context-dependent duality of MIR452—including a contribution to glioblastoma cell-state heterogeneity—thus positioning it as a promising diagnostic biomarker and therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "27"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Srinivas Veerla, David Lindgren, Anders Kvist, et al. 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