{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR-466 has emerged as a pivotal regulatory molecule with multifaceted roles across both oncologic and non‐oncologic conditions. In several cancers—including prostate, colorectal, osteosarcoma, gastric, and lung cancers—miR-466 is frequently downregulated, and its restoration has been shown to suppress tumor cell proliferation, migration, invasion, and metastasis. For instance, in prostate cancer, overexpression of miR-466 counteracts metastatic progression by targeting the bone‐related transcription factor RUNX2, whereas in colorectal cancer its increased expression correlates with cell cycle arrest, apoptosis induction, and reduced tumor aggressiveness."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistically, miR-466 exerts its tumor-suppressive function by directly targeting several key oncogenic factors. It downregulates proteins such as RUNX2 in prostate cancer, cyclin D1 and MMP-2 in colorectal cancer, and IRS1 in osteosarcoma, thereby influencing cell cycle progression, apoptotic pathways, and invasive behavior. These effects illustrate its critical role in maintaining cellular homeostasis and its potential as a prognostic biomarker in malignant contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond direct growth suppression, miR-466 is intricately involved in regulatory networks mediated by long non-coding RNAs. In prostate carcinoma and esophageal squamous cell carcinoma, oncogenic lncRNAs such as TUC338 and PGM5-AS1, respectively, function at least in part by sequestering miR-466, thus diminishing its suppressive effects and promoting cancer cell migration and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn non-malignant settings, members of the miR-466 family also demonstrate significant regulatory functions. During Coxsackie B virus infection, upregulation of rno-miR-466d (and its human ortholog) leads to reduced expression of the Coxsackie virus and Adenovirus Receptor (CAR), thereby potentially limiting viral entry."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Similarly, in the cortical collecting duct, aldosterone rapidly downregulates miR-466g to relieve its inhibitory effect on serum and glucocorticoid regulated kinase 1 (SGK1), a key kinase that upregulates epithelial sodium channel activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditionally, miR-466 modulates epithelial-to-mesenchymal transition (EMT) in intrauterine adhesion models by targeting NUS1 to affect cell proliferation, migration, and invasion, while in osteoblasts its family member miR-466f-3p, when sponged by the lncRNA NEAT1, impacts autophagy through regulation of hexokinase 2 (HK2)—a pathway relevant to osteoporosis pathogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn summary, the current body of evidence posits miR-466 as a versatile regulator whose tumor-suppressive functions across diverse cancers and modulatory roles in non-malignant processes highlight its potential as both a prognostic biomarker and a therapeutic target. Its capacity to directly inhibit oncogenic pathways while being influenced by lncRNA-mediated sponging underscores the complexity of its regulation and its far-reaching impact on cellular physiology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Melissa Colden, Altaf A Dar, Sharanjot Saini, et al. 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