{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nResearch across a broad spectrum of human cancers has revealed that MIR423 exhibits context‐dependent oncogenic functions. In hepatocellular carcinoma, for example, miR‑423‑3p is upregulated and promotes cell cycle progression at the G₁/S transition through direct inhibition of the tumor suppressor p21^Cip1/Waf1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In gastric cancer, exosome‑mediated transfer of miR‑423‑5p has been linked to enhanced proliferation, migration and metastasis via suppression of genes such as SUFU and TFF1, with complementary studies also implicating the miR‑423‑3p strand in regulating autophagy through Bim downregulation"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "7"}]}, {"type": "t", "text": ", and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In addition, studies in ovarian cancer have demonstrated that the long noncoding RNA LINC00319 functions as an endogenous sponge for miR‑423‑5p, thereby relieving repression of NACC1 and promoting tumor cell proliferation, migration and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Finally, analyses in papillary thyroid cancer, mantle cell lymphoma and oral squamous cell carcinoma have further underscored the clinical implications of MIR423 deregulation as both a functional driver and a potential prognostic biomarker."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn cardiovascular and metabolic disorders, circulating miR‑423 (predominantly the 5p strand) has emerged as a promising biomarker and functional mediator. In patients with acute myocardial infarction and chronic heart failure, elevated plasma levels of miR‑423‑5p correlate with impaired cardiac function and appear to modulate cardiomyocyte apoptosis through direct targeting of OGT"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": ", while analyses of pericardial fluid further support its utility as a cardiac marker."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": " Moreover, in metabolic liver disease associated with obesity and nonalcoholic fatty liver disease (NAFLD), miR‑423‑5p is upregulated in hepatocytes where it impairs the FAM3A–ATP–Akt pathway, thereby promoting gluconeogenesis and lipid accumulation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": ", with additional heart failure biomarker studies reinforcing its diagnostic relevance"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "and genetic studies linking MIR423 variants to coronary artery disease susceptibility further highlighting its multifaceted role."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond oncologic and cardiovascular contexts, MIR423 has been implicated in several other disorders. In reproductive and autoimmune settings, polymorphisms in the MIR423 precursor (such as rs6505162) are associated with increased mature MIR423 expression and heightened risk of recurrent pregnancy loss through modulation of PA2G4, and elevated circulating miR‑423‑5p has been observed in MuSK‑positive myasthenia gravis, potentially serving as a distinguishing biomarker."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": " In women with polycystic ovary syndrome, decreased miR‑423 levels in granulosa cells lead to impaired TGF‑β signaling via derepression of SMAD7."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": " In diabetic retinopathy, altered miR‑423 expression appears to regulate vascular endothelial growth factor (VEGF) and nitric oxide pathways, potentially impacting endothelial function and disease progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": " Finally, in lung adenocarcinoma and glioma, modulation of miR‑423‑5p levels alters tumor cell sensitivity to therapeutic agents—downregulation of miR‑423‑5p enhances the apoptotic response to apigenin in glioma stem cells, while in lung adenocarcinoma, sequestration by LOXL1‑AS1 leads to upregulation of the oncogene MYBL2—and stable expression in vulvar neoplasia has facilitated its use as a reference marker in gene expression studies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "25", "end_ref": "28"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jun Lin, Shenglin Huang, Shunquan Wu, et al. 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