{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMicroRNA‐599 functions as a tumor suppressor in several malignancies. In papillary thyroid carcinoma, for example, its downregulation leads to upregulation of the Hey2 gene and activation of the Notch signaling pathway, thereby promoting proliferation, migration, invasion, and epithelial–mesenchymal transition while inhibiting apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In osteosarcoma, miR‐599 directly binds TGFB2, with its overexpression reversing the enhanced proliferative and migratory capabilities driven by circ‑0000285."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Similar tumor‐suppressive functions have been reported in bladder cancer, where miR‐599 targets YAP1 as well as modulates the TOP2A axis to inhibit cell proliferation and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In breast cancer, two independent studies have demonstrated that miR‑599 targets E2F3 or BRD4—thereby interfering with oncogenic pathways such as Jagged1/Notch1—to diminish proliferation, migration, invasion, and glycolysis while promoting apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Finally, altered miR‑599 expression in cervical cancer has been correlated with prognosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond oncogenesis, miR‑599 plays important roles in non‐malignant conditions. In Parkinson’s disease, it targets LRRK2, suggesting a potential inhibitory effect on disease progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In patients with ischemic stroke, altered serum levels of miR‑599 correlate with inflammatory markers such as hs‑CRP and MMP‑9."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In vascular contexts, miR‑599 overexpression protects endothelial cells from lipopolysaccharide‑induced apoptosis and inflammation by downregulating ROCK1 and blunting JAK2/STAT3 signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " In osteoarthritis, miR‑599 targets Casz1, thereby promoting chondrocyte apoptosis and inflammation—a process that is mitigated by circANKRD36 sponging of miR‑599."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Moreover, regulation of miR‑599 has been implicated in cell heterogeneity and endothelial–mesenchymal transition in aortic valve stromal cells via the TGF‑β pathway"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", and circ_0000285‐mediated modulation of miR‑599 may influence vascular smooth muscle cell injury in abdominal aortic aneurysm."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " In addition, genetic studies in patients with cirrhosis have begun to explore how related regulatory networks might impact acute kidney injury."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Duo-Ping Wang, Xiao-Zhun Tang, Quan-Kun Liang, et al. 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