{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMiR‑370 has emerged as a context‐dependent regulator in a wide array of cancers. In cholangiocarcinoma, interleukin‑6 induces DNA hypermethylation that silences miR‑370, thereby restoring the expression of MAP3K8 and promoting tumor cell growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In gastric carcinoma, miR‑370 is found overexpressed in tissues and plasma where it targets transforming growth factor‑β receptor II, correlating with advanced nodal metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Studies in hyperlipidemia‐associated coronary artery disease and acute myeloid leukemia have also underscored miR‑370 dysregulation in pathological conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In prostate cancer, increased miR‑370 promotes proliferation by directly downregulating the tumor suppressor FOXO1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", while in cholangiocarcinoma elevated interleukin‑6 also silences miR‑370 through hypermethylation of its imprinting control region, contributing to aberrant WNT signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In the context of Helicobacter pylori–induced gastric pathologies, miR‑370 reduction leads to increased FoxM1 levels and diminished cell‐cycle inhibitor expression"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", whereas in another gastric cancer study, its overexpression was linked to FOXO1 suppression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In hepatocellular carcinoma, miR‑370 acts as a tumor suppressor by targeting the RNA‐binding protein LIN28A, and in laryngeal squamous cell carcinoma its low expression is associated with increased FoxM1 levels."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Moreover, studies have described miR‑370 dysregulation in lung adenocarcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", in endometrioid ovarian cancer where it suppresses endoglin to reduce cellular viability"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", in enterovirus‑71 infection by targeting GADD45β to mitigate apoptosis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ", and in non‑small cell lung cancer where its low levels lead to reduced inhibition of TRAF4."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Observations in metabolic disorders further expand its clinical relevance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond cancer, miR‑370 influences diverse biological processes. In osteoarthritis, it is downregulated in chondrocytes where its restoration reduces matrix‐degrading enzymes by targeting SHMT‑2"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": ", and in osteosarcoma, miR‑370 suppresses FOXM1 to inhibit proliferation and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": " Although its expression in acute myeloid leukemia shows controversy"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": ", in colorectal cancer miR‑370 suppresses critical oncogenic signaling by targeting EGFR and PIK3CA"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": ", and in glioma lower levels of miR‑370‑3p have been associated with aggressive disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": " In bladder cancer, reductions in miR‑370—partly mediated by interleukin‑6–induced DNMT1 overexpression—result in elevated SLD5 expression, fostering tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": " In gastric cancer, another report indicated that miR‑370 targets PTEN, thereby modulating the AKT cascade"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": ", while in glioblastoma, restoration of miR‑370‑3p increases chemosensitivity through MGMT suppression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": " Its regulatory spectrum even extends to controlling the expression of drug‐metabolizing enzyme CYP2D6 via mRNA degradation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": "and to mediating dsRNA‐induced gene activation such as that of p21."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "25"}]}, {"type": "t", "text": " Additionally, in esophageal squamous cell carcinoma, miR‑370 downregulates PIN1 to inhibit cell growth"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "26"}]}, {"type": "t", "text": ", while in models of atherosclerosis it mitigates inflammatory signaling and reactive oxygen species production by targeting TLR4."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "27"}]}, {"type": "t", "text": " In the context of neurodegenerative disorders such as spinocerebellar ataxia type 3, miR‑370 targets DNAJB1, suggesting its broader involvement in protein quality control."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "28"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMiR‑370 also plays a key role in intercellular communication and is subject to regulation by non‑coding RNAs. In gastric cancer, it downregulates PAQR4 expression to inhibit proliferation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "29"}]}, {"type": "t", "text": ", and in endometriosis, reduced miR‑370 levels lead to SF‑1–driven steroidogenic overactivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "30"}]}, {"type": "t", "text": " Though studies in bone marrow–derived mesenchymal stem cells underscore the importance of lncRNA networks"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "31"}]}, {"type": "t", "text": ", in breast cancer miR‑370 has been shown to function as an oncogene by downregulating WNK2, thereby promoting tumor growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "32"}]}, {"type": "t", "text": " While certain investigations in non‑small cell lung cancer and related systems hint at additional layers of regulatory complexity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "33"}]}, {"type": "t", "text": ", in models of acute pneumonia preliminary data extend its involvement"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "35"}]}, {"type": "t", "text": "—and, in endometriosis, further studies confirmed miR‑370’s suppression of SF‑1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "36"}]}, {"type": "t", "text": " In sepsis, links between lncRNA NEAT1 and miR‑370 hint at immune‐regulatory roles"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "37"}]}, {"type": "t", "text": ", while in cisplatin‑resistant esophageal cancer, a circular RNA sequesters miR‑370‑3p to upregulate Wnt7a and promote chemoresistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "38"}]}, {"type": "t", "text": " In glioblastoma, miR‑370‑3p acts as a tumor suppressor by targeting oncogenic lncRNAs including NEAT1 as well as HMGA2 and HIF1A"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "39"}]}, {"type": "t", "text": ", and in atherosclerosis it also modulates HMGB1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "40"}]}, {"type": "t", "text": " In breast cancer, extracellular vesicles deliver miR‑370‑3p to normal fibroblasts where it downregulates CYLD and activates NF‑κB signaling"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "41"}]}, {"type": "t", "text": ", and in diffuse large B‑cell lymphoma a long non‑coding RNA sponge defines a miR‑370‑3p/CBX3 axis that promotes proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "42"}]}, {"type": "t", "text": " Finally, in metastatic breast cancer, circRNAs such as circFOXK2 have been implicated in sequestering miR‑370 to promote invasion, and in ovarian cancer, emerging evidence further supports miR‑370’s involvement in tumorigenic pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "43"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "F Meng, H Wehbe-Janek, R Henson, et al. 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