{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR‑1303 is a multifunctional microRNA whose dysregulated expression has been implicated in a spectrum of pathological conditions. In metabolic and vascular disorders, for example, miR‑1303 is found upregulated in the serum of type 2 diabetes mellitus patients with microvascular complications, supporting its use not only as a diagnostic biomarker but also as a potential contributor to vascular injury. In contrast, during coxsackievirus A16 infection—a model for hand, foot and mouth disease—miR‑1303 expression is downregulated, which results in increased matrix metalloproteinase‑9 (MMP9) levels, the degradation of tight junction proteins, and consequent blood–brain barrier disruption. Altered circulating profiles of miRNAs, including miR‑1303, have also been observed in head and neck cancers, underscoring its emerging role in disease diagnostics."}, {"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 oncological contexts, miR‑1303 exhibits context‑dependent functions by modulating key regulators of tumor cell behavior. In gastric cancer, for instance, miR‑1303 appears to promote tumorigenesis by directly targeting claudin‑18. Similarly, in neuroblastoma its upregulation fosters proliferation through inhibition of tumor suppressors such as glycogen synthase kinase 3β and secreted frizzled‑related protein 1. Aberrant miR‑1303 expression is also linked with non‑small cell lung cancer and liver cancer progression, highlighting its potential as a therapeutic target. Moreover, in osteosarcoma, reduced levels of miR‑1303—resulting from the sponging actions of long non‑coding RNAs (e.g., BCRT1) and circular RNAs—lead to increased fibroblast growth factor 7 (FGF7) expression and activation of metastasis‑promoting pathways, including those involving apelin‑mediated upregulation of the collagen cross‑linking enzyme PLOD2."}, {"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": "\nBeyond its roles in disease, miR‑1303 is also modulated by physiological and therapeutic stimuli. Regular physical exercise—as observed in veteran football players—affects miR‑1303 expression in skeletal muscle, suggesting its involvement in longevity pathways and metabolic adaptations. In cardiomyocytes, downregulation of miR‑1303 due to sponging by circ‑SKA3 leads to upregulation of toll‑like receptor 4 (TLR4) and contributes to doxorubicin‑induced cardiotoxicity. In addition, emerging RNA‑therapeutic strategies and comprehensive profiling studies in conditions such as osteoporosis and liver cancer have underscored the complex regulatory networks that involve miR‑1303, highlighting its potential as a target for future intervention."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lokman Ayaz, Aysegül Görür, Hatice Yıldırım Yaroğlu, et al. 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