{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMiR-422a functions predominantly as a tumor suppressor across a broad spectrum of human malignancies. In hepatocellular carcinoma, reduced miR-422a expression is associated with advanced pathological grading and metastasis, with restoration of its levels inhibiting tumor cell proliferation and migration via direct targeting of forkhead box family transcripts ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "]. In colorectal cancer, lowered miR-422a correlates with increased clinical stage and poor prognosis, and its re‐expression has been shown to arrest the G1/S transition by suppressing cell cycle regulators ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "]. Similar tumor‐inhibitory functions have been reported in gastric cancer where miR-422a overexpression disrupts aerobic glycolysis by targeting pyruvate dehydrogenase kinase 2, and in head and neck squamous cell carcinoma where loss of miR-422a leads to upregulation of CD73/NT5E and early loco-regional relapse ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "]. In osteosarcoma, enforced miR-422a expression suppresses cell proliferation and invasion while promoting apoptosis and cell cycle arrest through inhibition of TGFβ2 as well as regulators such as BCL2L2 and KRAS ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "]. In glioma, miR-422a significantly hampers tumor growth by targeting both IGF1/IGF1R and ribophorin II, thereby dampening downstream pro-tumorigenic signals ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "]. Moreover, in esophageal squamous cell carcinoma and retinoblastoma, oncogenic circular RNAs (such as circUBAP2 and circ_ODC1) sequester miR-422a—thereby releasing targets like Rab10 and SKP2 that drive tumor progression ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "]. The malignant phenotype is further supported in glioblastoma and non-small cell lung cancer, where long noncoding RNAs (e.g., NORAD) or circular RNAs (e.g., circNT5E) sponge miR-422a to impair its suppressive function ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "]."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "12"}, {"type": "fg_f", "ref": "11"}, {"type": "fg_f", "ref": "10"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "Disrupted miR-422a signaling is not confined to oncogenesis but extends to diverse physiological and pathological processes. In hepatic tissue, miR-422a binds to the 3′-untranslated region of CYP7A1 mRNA, thereby modulating bile acid synthesis ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "]. Circulating miR-422a, notably enriched in plasma exosomes, serves as a promising predictive biomarker—not only for ischemic stroke ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "] but also for lymphatic metastasis in lung cancer ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "]. In diabetic nephropathy, high-glucose conditions induce the secretion of exosomal circRNAs that sponge miR-422a, leading to dysregulation of the IGF1R/p38 signaling axis and promoting mesangial cell proliferation and fibrosis ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": "]. Furthermore, miR-422a influences bone metabolism by regulating the adipogenic differentiation of human bone marrow mesenchymal stromal cells via MeCP2 downregulation, with reduced circulating levels being linked to bone mass loss in postmenopausal osteoporosis ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "]. Notably, in the nervous system, miR-422a targets the DCC netrin 1 receptor; its morphine-induced downregulation implicates a potential role in opioid addiction ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": "], while in the lung, extracellular vesicle-mediated networks involving miR-422a and SPP1 have been linked to the attenuation of smoking-induced chronic obstructive pulmonary disease ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": "]."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}, {"type": "fg_f", "ref": "16"}, {"type": "fg_f", "ref": "15"}, {"type": "fg_f", "ref": "20"}, {"type": "fg_fs", "start_ref": "17", "end_ref": "19"}, {"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": "In summary, the multifaceted regulatory functions of miR-422a—ranging from direct repression of oncogenic drivers and metabolic enzymes to its modulation through competing endogenous RNAs—underscore its critical role in tumor suppression, metabolic homeostasis, and cellular differentiation. These insights not only highlight miR-422a’s promise as a prognostic biomarker across diverse diseases but also suggest that therapeutic strategies aimed at restoring or mimicking its function may offer broad clinical benefit."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}, {"type": "fg_f", "ref": "10"}, {"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jin Zhang, Yun Yang, Tian Yang, et al. 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