{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMicroRNA MIR520D isoforms, including both the –3p and –5p strands, have been implicated in a variety of cellular processes across diverse pathological conditions. For instance, MIR520D was found to be significantly up-regulated in chronic periodontitis tissues relative to healthy gingiva, suggesting a potential role in inflammatory responses and disease progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In multiple cancer types, MIR520D exhibits tumor‐suppressive properties: in gastric cancer, the –3p strand is down-regulated and its restoration suppresses proliferation, migration, and invasion by targeting the EphA2 gene"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "; in hepatocellular carcinoma and osteosarcoma, similar down-regulation is observed with re-expression inhibiting tumor growth and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in inhibiting tumor progression through direct targets, the MIR520D family exerts complex regulatory effects on metastasis. The –5p strand has been reported to target key modulators such as TWIST1, leading to decreased miR-10b levels, restoration of E-Cadherin expression, and ultimately reduced cellular invasiveness and proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Similarly, in cervical cancer, MIR520D-5p is shown to regulate expression of several genes implicated in tumor development"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", while in melanoma, downregulation of MIR520D-3p correlates with increased expression of ASF1B, a gene whose targeting by MIR520D-3p leads to suppression of tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOutside of the oncological context, MIR520D also plays roles in other diseases. In Parkinson's disease, elevated levels of the –5p form in serum were linked to reduced ceruloplasmin gene expression, potentially contributing to disruptions in brain iron metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In astrocytoma, both MIR520D-3p and –5p are associated with modulation of SIRPα expression, a protein involved in immune interactions, with expression patterns correlating with tumor grade."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Moreover, MIR520D-5p has been observed to revert undifferentiated hepatoma cells toward a more benign state by inducing demethylation and upregulating P53"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", and in myocardial cells subjected to hypoxia/reoxygenation injury, overexpression of MIR520D-3p attenuates cell viability loss and apoptosis through partial regulation of autophagy via ATG12."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Finally, within the context of infectious disease, the MIR520D family (sharing its seed sequence with MIR372 and MIR373) modulates arginine metabolism in human macrophages by targeting the arginine transporter SLC7A2, thereby influencing polyamine production and facilitating Leishmania survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Young Hwa Lee, Hee Sam Na, So Yeon Jeong, et al. 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