{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR‐192 plays multifaceted roles in tumor biology, acting in many contexts as a mediator of p53‐dependent cell cycle arrest and apoptosis. For example, miR‐192 is induced by genotoxic stress to promote growth‐inhibitory signals and tumor suppression in colon cancer cells"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", and its investigation in colon cancer has further underscored its involvement in modulating key cell cycle regulators."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In colorectal cancer cell lines, miR‐192 (often coupled with its homolog miR‐215) down‐regulates thymidylate synthase and induces cell cycle arrest"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", whereas in gastric cancer, overexpression of miR‐192 correlates with increased cell growth and migration by modulating the levels of adhesion molecules."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In lung cancer models, elevated miR‐192 expression suppresses proliferation and initiates apoptosis via targeting of retinoblastoma 1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", and in breast cancer cells, stimulation of miR‐192 by BMP‐6 enforces cell cycle arrest through repression of RB1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "&."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Furthermore, in metastatic colon cancer models, miR‐192 inversely correlates with aggressive phenotypes by lowering the expression of anti‐apoptotic and pro‐angiogenic targets such as Bcl‐2, Zeb2 and VEGFA"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", while studies in bladder cancer support its tumor suppressor function by inhibiting proliferation and fostering apoptosis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "&."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " In addition, miR‐192 overexpression in bladder cancer has been associated with reduced cyclin D1 and increased levels of cell cycle inhibitors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in classical neoplastic settings, miR‐192 is critically involved in the regulation of renal and metabolic disorders. In diabetic nephropathy, diminished miR‐192 expression in proximal tubular cells correlates with increased fibrosis and impaired kidney function"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", while altered levels in serum have been linked with systemic autoimmune disorders such as systemic lupus erythematosus."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Moreover, TGF‐β signaling appears to modulate miR‐192 expression in the kidney through p53 and hepatocyte nuclear factor–dependent mechanisms"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": ", and studies in pancreatic ductal adenocarcinoma (PDAC) have reported elevated serum miR‐192 that promotes tumor cell proliferation by repressing SIP1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": " In hepatocellular as well as HCV‐associated disease, miR‐192 serves as a potential biomarker for progression from fibrosis to carcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": ", and in certain hepatocellular carcinoma (HCC) models, dysregulated miR‐192 may in fact promote metastatic behavior by influencing targets such as SEMA3A."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": " Other investigations in diabetic kidney disease have noted altered miR‐192 profiles"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "&"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": ", and in PDAC, epigenetic silencing of miR‐192 is linked to enhanced invasion"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": ", while further patient studies in diabetic nephropathy continue to emphasize its diagnostic relevance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": " In chronic lymphocytic leukemia, reduced miR‐192 has been associated with loss of cell cycle control"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": ", and in hypertensive models, higher kidney miR‐192‐5p expression appears protective by attenuating Na+/K+–ATPase activity through ATP1B1 targeting"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": "&."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": " Additionally, in rheumatoid arthritis, restoration of miR‐192 reduces synoviocyte proliferation and inflammation via direct repression of caveolin 1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence further implicates miR‐192 in the modulation of diverse pathological conditions. Its altered levels have been observed in investigations of leptomeningeal dissemination in pediatric brain tumors"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "26"}]}, {"type": "t", "text": ", as well as in non‐alcoholic fatty liver disease and related metabolic disorders"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "27"}]}, {"type": "t", "text": "&."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "28"}]}, {"type": "t", "text": " In hepatocellular carcinoma, reduced miR‐192‐5p within cancer stem cell populations correlates with enhanced stemness via derepression of PABPC4."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "29"}]}, {"type": "t", "text": " Moreover, circulating miR‐192 has been proposed as an early biomarker in acute ischemic stroke"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "30"}]}, {"type": "t", "text": ", while in asthma, down‐regulation of miR‐192‐5p contributes to airway smooth muscle proliferation by modulating MMP‐16 and ATG7."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "31"}]}, {"type": "t", "text": " In sepsis‐induced myocardial injury, the lncRNA KCNQ1OT1 regulates miR‐192‐5p to control cardiomyocyte apoptosis via the XIAP axis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "32"}]}, {"type": "t", "text": ", and in diabetic retinopathy, mesenchymal stem cell–derived extracellular vesicles shuttle miR‐192 to dampen inflammation and angiogenesis through ITGA1 inhibition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "33"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sara A Georges, Matthew C Biery, Soo-Yeon Kim, et al. 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