{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have demonstrated that miR-556, including its −5p and −3p isoforms, plays versatile roles in both non‐malignant diseases and cancer. In systemic lupus erythematosus, miR-556-5p has been identified as a promising diagnostic biomarker for lupus nephritis, suggesting that its altered expression may reflect renal involvement and associated pathology. In clear cell renal cell carcinoma, a polymorphism within the GSTM3 3′UTR that interferes with miR-556 binding modulates GSTM3 protein levels, thereby influencing reactive oxygen species clearance and disease susceptibility. Similarly, in an in vitro model of oxidized low-density lipoprotein–induced injury in endothelial cells, increased miR-556-5p expression contributes to impaired angiogenesis and heightened oxidative stress through repression of TET2."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn various cancer types, miR-556 functions predominantly as an oncogenic regulator. In prostate cancer, upregulation of miR-556-5p drives cell proliferation via downregulation of the tumor suppressor PPP2R2A, resulting in cell cycle dysregulation. In bladder cancer, direct targeting of the tumor suppressor DAB2IP by miR-556-3p activates Ras-ERK signaling to promote proliferation, invasion, and metastasis. Enhanced miR-556-3p expression has also been implicated in esophageal cancer progression, while in cisplatin-resistant non-small cell lung cancer, elevated miR-556-5p levels underpin chemoresistance by attenuating NLRP3-mediated pyroptosis. Moreover, in breast cancer a feedback loop—where KIAA1429-induced m6A modification of LINC00667 sequesters miR-556-5p—further promotes tumor growth, and in hepatocellular carcinoma, restoration of DAB2IP expression through inhibition of miR-556-3p can counteract epithelial–mesenchymal transition and metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe activity of miR-556 is further fine-tuned by interactions with competing endogenous RNAs in several tumor contexts. In meningioma, overexpressed lncRNA SNHG1 acts as a molecular sponge for miR-556-5p to relieve its inhibition on the downstream target TCF12, thereby promoting cell proliferation via activation of the Wnt signaling pathway. In hemangioma‐derived endothelial cells, elevated miR-556-3p suppresses VEGFC expression, favoring increased cell viability and reduced apoptotic response. In osteosarcoma, circ_0096041 sequesters miR-556-5p, which otherwise targets the oncogene LIN28A, resulting in enhanced tumor cell proliferation and migration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Elkin Navarro-Quiroz, Lisandro Pacheco-Lugo, Hernan Lorenzi, et al. 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