{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n AGAP2‐AS1 is emerging as a multifunctional long noncoding RNA that plays an oncogenic role in a wide spectrum of human diseases, particularly in cancer. Elevated levels of AGAP2‐AS1 have been reported in non‐small cell lung cancer, gastric cancer, pancreatic cancer, glioma, glioblastoma, colorectal cancer, papillary thyroid carcinoma, ovarian carcinoma, and laryngeal as well as clear cell renal cell carcinomas, where its high expression correlates with advanced tumor stage, metastasis, poor prognosis, and resistance to therapy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": " In contrast, at least one study in epithelial ovarian cancer has demonstrated decreased AGAP2‐AS1 levels associated with more aggressive clinical features, underscoring potential tissue‐specific functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Mechanistically, AGAP2‐AS1 exerts its oncogenic activity by a variety of means. In several cancer types, it functions as a competing endogenous RNA that sequesters tumor‐suppressive microRNAs—including miR‐15a/b‐5p, miR‐628-5p, miR‐424-5p, miR‐497, and miR‐182-5p—thereby releasing the inhibition on target oncogenic proteins such as HDGF, KLF12, LOXL4, and CFL1."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "14"}]}, {"type": "t", "text": " Additionally, AGAP2‐AS1 has been reported to recruit epigenetic modifiers such as EZH2 and LSD1 to target promoter regions, leading to the transcriptional repression of tumor‐suppressor genes, including KLF2, LATS2, CDKN1A (p21), and E-cadherin."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In colon cancer, feedback interactions with other long noncoding RNAs (for example, LINC-PINT) and modulation of Hippo signaling have been implicated in its pro-proliferative and pro-metastatic effects."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond proliferation, AGAP2‐AS1 contributes to therapeutic resistance. In HER2‐positive breast cancer, its upregulation—partially driven by mesenchymal stem cell interactions—is associated with trastuzumab resistance through its incorporation into exosomes and stabilization of metabolic enzymes such as CPT1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}, {"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": " Similarly, in lung cancer, AGAP2‐AS1 is linked to radioresistance via modulation of the miR‐296/NOTCH2 axis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Moreover, extracellular vesicle-associated AGAP2-AS1 has been shown to promote cervical cancer cell growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Meta-analyses and gene expression profiling across diverse tumors reinforce the clinical significance of AGAP2‐AS1 as a biomarker predictive of overall survival, disease-free survival, and advanced clinicopathological features."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": " Beyond cancer, dysregulation of AGAP2‐AS1 has been observed in diseases such as psoriasis—where it promotes keratinocyte proliferation via the miR‐424-5p/AKT3 axis—and systemic sclerosis, suggesting a broader role in regulating cell proliferation and apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": " Additionally, AGAP2‐AS1 forms part of prognostic signatures in anaplastic gliomas"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": ", further highlighting its potential as a therapeutic target and biomarker.\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, AGAP2‐AS1 acts as a critical regulator of oncogenic processes through its effects on microRNA sponging, epigenetic modulation, and signal transduction. Its dysregulation not only promotes cell proliferation, migration, invasion, and resistance to apoptosis, but also contributes to therapeutic resistance by facilitating intercellular communication. These diverse functions position AGAP2‐AS1 as a promising biomarker for diagnosis, prognosis, and as a potential target for future therapeutic interventions in cancer and other proliferative diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}, {"type": "fg_f", "ref": "11"}, {"type": "fg_fs", "start_ref": "4", "end_ref": "6"}, {"type": "fg_f", "ref": "22"}, {"type": "fg_fs", "start_ref": "7", "end_ref": "9"}, {"type": "fg_f", "ref": "16"}, {"type": "fg_f", "ref": "13"}, {"type": "fg_f", "ref": "21"}, {"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "W Li, M Sun, C Zang, et al. 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