{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Long noncoding RNA ARAP1‑AS2 is emerging as an important regulator in diabetes and diabetic kidney disease. Studies have shown that its circulating levels progressively increase in patients with diabetes and diabetic nephropathy, in parallel with the upregulation of its target gene ARAP1, suggesting a potential role as a biomarker for these conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In vitro experiments in human renal proximal tubular (HK‑2) cells under high‐glucose conditions demonstrated that ARAP1‑AS2 overexpression significantly enhances the epithelial–mesenchymal transition (EMT) process by promoting cytoskeletal rearrangement, increased cell viability, migration, and elevated Cdc42‑GTP levels."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, ARAP1‑AS2 directly interacts with ARAP1 to modulate EGFR ubiquitination, thereby sustaining persistent EGFR activation and triggering downstream TGF‑β/Smad3 signaling, which further contributes to fibrosis and cell proliferation in diabetic contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " A systematic review of diabetic kidney disease patients has also identified ARAP1‑AS2 among a group of dysregulated lncRNAs associated with the disease, reinforcing its potential clinical relevance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ying Yang, Xiaomeng Lv, Qiuling Fan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of circulating lncRNA expression profiles in patients with diabetes mellitus and diabetic nephropathy: Differential expression profile of circulating lncRNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Nephrol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.5414/CN109525"}], "href": "https://doi.org/10.5414/CN109525"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31079598"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31079598"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lulu Li, Li Xu, Si Wen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The effect of lncRNA-ARAP1-AS2/ARAP1 on high glucose-induced cytoskeleton rearrangement and epithelial-mesenchymal transition in human renal tubular epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.29512"}], "href": "https://doi.org/10.1002/jcp.29512"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31975379"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31975379"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xin Li, Tian-Kui Ma, Si Wen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA ARAP1-AS2 promotes high glucose-induced human proximal tubular cell injury via persistent transactivation of the EGFR by interacting with ARAP1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.15897"}], "href": "https://doi.org/10.1111/jcmm.15897"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32969198"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32969198"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yunyun Zhao, Guanchi Yan, Jia Mi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Impact of lncRNA on Diabetic Kidney Disease: Systematic Review and In Silico Analyses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Comput Intell Neurosci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2022/8400106"}], "href": "https://doi.org/10.1155/2022/8400106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35528328"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35528328"}]}]}]}