{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CTBP1‐AS2 is a multifunctional long noncoding RNA whose dysregulation has been implicated in diverse disease settings. In metabolic disorders, altered CTBP1‐AS2 expression has been associated with diabetes. For instance, in diabetic nephropathy models, overexpression of CTBP1‐AS2 attenuates high glucose–induced proliferation, oxidative stress, extracellular matrix deposition, and inflammatory responses via modulation of the miR‐155‐5p/FOXO1 signaling axis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, reduced levels of CTBP1‐AS2 in peripheral blood cells have been linked with type 2 diabetes susceptibility, indicating its potential as a predictive biomarker."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of musculoskeletal disorders, CTBP1‐AS2 is upregulated in osteoarthritis, where it appears to suppress chondrocyte proliferation by promoting methylation‐mediated downregulation of miR‑130a."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In cancers, CTBP1‐AS2 mainly acts as an oncogenic regulator through its activity as a competing endogenous RNA that sponges distinct microRNAs. In hepatocellular carcinoma, it sequesters miR‑195‑5p to relieve inhibition of CEP55 expression, thereby facilitating tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Similarly, in glioma its upregulation promotes epithelial–mesenchymal transition (EMT) and cell migration via a regulatory circuit involving miR‑370‑3p and Wnt7a."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " CTBP1‐AS2 is also elevated in breast cancer tissues, where its diagnostic performance appears promising."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In pancreatic carcinoma, CTBP1‐AS2 enhances proliferation, migration, invasion, and chemoresistance by sponging miR‑141‑3p to upregulate USP22 expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In non‐small cell lung cancer, overexpression of CTBP1‐AS2 promotes cell growth, cell cycle progression, and EMT by suppressing miR‑623 and thereby increasing MMP3 expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, in cervical cancer, CTBP1‐AS2 acts as a molecular sponge for miR‑3163 to elevate ZNF217 levels, which in turn enhances tumor proliferation, migration, and invasion"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", and in gastric cancer its high expression is associated with increased cell proliferation and metastasis through regulation of miR‑139‑3p–mediated pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond cancer, CTBP1‐AS2 is involved in cardiovascular pathologies. In cardiomyocyte hypertrophy, for example, CTBP1‐AS2 is upregulated under stress conditions and promotes hypertrophy by stabilizing TLR4 mRNA through FUS recruitment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " In atherosclerosis, its expression in vascular smooth muscle cells is linked to inhibition of proliferation and promotion of autophagy via a miR‑195‑5p/ATG14 regulatory axis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings highlight CTBP1‐AS2 as a pivotal regulator that, predominantly by acting as a microRNA sponge, contributes to the modulation of key signaling pathways involved in cell proliferation, differentiation, inflammation, and apoptosis across a variety of disease contexts. Its diverse roles underscore its potential not only as a diagnostic biomarker but also as a promising therapeutic target.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Guang Wang, Bing Wu, Bo Zhang, et al. 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