{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR-939 is emerging as a multifunctional regulator whose role spans diverse pathological settings, particularly in human cancers. In triple‐negative breast cancer, miR-939 is secreted via exosomes and directly targets VE-cadherin, thereby weakening endothelial cell–cell junctions and facilitating metastatic transit (via increased vascular permeability)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In ovarian cancer, upregulation of miR-939 promotes cell proliferation and anchorage‐independent growth by directly suppressing the tumor suppressor APC2 and, in non–small cell lung cancer, miR-939 downregulation leads to a significant decline in proliferation and invasion via modulation of TIMP2."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "5"}]}, {"type": "t", "text": " Similarly, in glioma, increased levels of miR-939-5p correlate with enhanced proliferation, migration, and invasion through targeting TIMP2, collectively underscoring its context-dependent dual roles as both oncogene and tumor suppressor depending on the cancer type."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the cardiovascular and inflammatory arenas, miR-939 also plays a key regulatory role. In myocardial ischemia, exosomes from affected patients show significant downregulation of miR-939-5p, thereby releasing its inhibitory effect on inducible nitric oxide synthase (iNOS) and promoting angiogenesis and tissue repair."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In vascular smooth muscle cells, reduced miR-939 levels are linked with a phenotypic shift that favors proliferation and migration through the de-repression of targets such as STIM1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", while in hepatocytes, miR-939 targets the 3′-UTR of hiNOS to impose a translational blockade, ensuring a balanced nitric oxide output."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Moreover, in inflammatory conditions including complex regional pain syndrome, downregulation of miR-939 corresponds with elevated proinflammatory mediator expression, further emphasizing its critical regulatory function. In coronary artery disease, overexpression of miR-939 in endothelial cells inhibits adhesion, proliferation, and tube formation by directly targeting γ-catenin, and in chronic heart failure, elevated serum miR-939-5p modulates cytokine-induced apoptosis in endothelial and myocardial cells."}, {"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": "\nBeyond oncogenic and cardiovascular regulation, miR-939 is involved in diverse biological processes affecting host–pathogen interactions and cellular homeostasis. In chronic hepatitis B infection, miR-939 exerts antiviral activity by targeting host factor Jmjd3, which in turn alters the transcriptional activity of viral promoters."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Its upregulation in Hirschsprung's disease is linked to reduced cell proliferation through targeting LRSAM1, while in neuronal cells, miR-939 directly suppresses the expression of the nerve growth factor receptor (NGFR), affecting cell survival pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": " In kidney podocytes, miR-939 binds to promoter sequences of CD2AP, contributing to reduced expression of this slit diaphragm component and implicating it in podocyte injury."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": " Finally, preliminary investigations in the context of influenza virus infection have explored the impact of miR-939 on viral replication, further highlighting its versatile regulatory portfolio."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Martina Di Modica, Viola Regondi, Marco Sandri, et al. 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