{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nStudies in viral infections have revealed that MIR576 variants play key roles in modulating host–pathogen interactions. In influenza‐infected patients, dysregulation of MIR576‐3p was identified in whole blood, suggesting its potential as a biomarker as well as a modulator of host proteome changes (a role that may extend to the regulation of gene networks during infection)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In cells infected with vesicular stomatitis virus and other RNA and DNA viruses, MIR576‐3p is induced by IRF3 in parallel with interferon production and acts in a negative feedback loop by targeting innate immune adaptors such as STING, MAVS, and TRAF3, thereby fine‐tuning and preventing an overzealous inflammatory response."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " A related study on Oropouche virus infection further demonstrated that early upregulation of MIR576‐3p contributes to viral replication by modulating targets involved in the interferon‐mediated response."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn cancer contexts, MIR576 exhibits multifaceted functions that appear to be highly context dependent. In bladder cancer, overexpression of MIR576‐3p induces G1‐phase arrest by directly targeting cyclin D1, curbing cell proliferation; its potential prognostic value has also been documented in patient studies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In contrast, in non‐small cell lung cancer, elevated MIR576‐5p expression contributes to tumor progression by downregulating the tumor suppressor ITGBL1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", while in esophageal squamous cell carcinoma it, along with miR‑548‑3p, promotes cell migration and invasion through inhibition of NRIP1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In glioblastoma, forced expression of MIR576‑3p restrains cell migration and angiogenesis via direct targeting of hypoxia‑inducible factor‑1α."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, in esophageal cancer, the LINC‑PINT–MIR576‑5p pathway has been implicated in the inhibition of tumor cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In ovarian cancer, upregulation of MIR576‑3p increases cisplatin chemosensitivity by downregulating PD‑L1 and cyclin D1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Conversely, high expression of MIR576‑5p in colorectal cancer enhances epithelial–to–mesenchymal transition and metastasis by interacting with Wnt5a to regulate Wnt/β‑catenin signaling"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", and in gastric cancer, oncogenic activity mediated by MIR576‑5p is counteracted by LINC01133, which upregulates somatostatin to suppress tumor growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " In breast cancer, the oncogenic axis involving circ_0012673 sponges MIR576‑3p to stabilize SOX4, thereby promoting proliferation, migration, and invasion"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "; additionally, MIR576‑5p has been implicated in the development of endometrial cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Finally, in renal cell carcinoma, MIR576 emerges as a novel biomarker candidate by virtue of its predicted regulation of targets such as CUL3 and RAC1, which are involved in cancer‐related pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond infectious and neoplastic settings, MIR576‐3p is also involved in vascular pathology. In atherosclerosis, for instance, the circular RNA circ_0086296 acts as a sponge for MIR576‑3p, leading to the upregulation of IFIT1 and STAT1 and thereby promoting endothelial cell injury and lesion progression—this establishes a feedback loop that accentuates inflammatory responses within vessel walls."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Paul A Tambyah, Sugunavathi Sepramaniam, Jaminah Mohamed Ali, et al. 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