{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Long non‐coding RNA gastric cancer‐associated transcript 3 (GACAT3) has emerged as an oncogenic regulator in multiple human malignancies. In various cancers including breast, glioma, colorectal, gastric, esophageal, non‐small cell lung, and bladder cancers, GACAT3 is frequently up‐regulated and its high expression is correlated with poor clinical outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " Functionally, GACAT3 promotes cell proliferation, migration, invasion, and inhibits apoptosis. Mechanistically, it acts mainly as a competing endogenous RNA (ceRNA) by “sponging” specific microRNAs, thereby de‐repressing their target oncogenes. For instance, in breast cancer and glioma, GACAT3 sponges miR‑497 and miR‑3127‑5p respectively to upregulate targets such as cyclin D2 and ELAVL1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "; similarly, in esophageal squamous cell carcinoma and colorectal cancer, it sequesters miR‑149, leading to enhanced expression of FOXM1, SP1, and STAT3."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In non‑small cell lung cancer, GACAT3 overexpression not only stimulates tumor cell aggressiveness but also modulates radiosensitivity via regulation of TIMP2 and downstream MMP10."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Beyond its role in cancers, elevated GACAT3 levels have been implicated in osteoarthritis by promoting synoviocyte proliferation through the IL‑6/STAT3 pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In gastric cancer, GACAT3 functions as a ceRNA for oncogenic factors such as HMGA1 and is up‑regulated downstream of IL‑6/STAT3 signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In glioma, it further promotes tumor progression by sponging miR‑135a to regulate the expression of NAMPT"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", and in bladder cancer, targeting of GACAT3 leads to increased expression of cell cycle and apoptosis regulators such as p21, Bax, and E‑cadherin."}, {"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 indicate that GACAT3 plays a multifaceted oncogenic role by modulating key signaling pathways and gene expression networks via a ceRNA mechanism. Its dysregulation contributes to enhanced tumor cell growth, metastasis and resistance to therapy, suggesting that it might serve as a promising diagnostic biomarker and a potential therapeutic target in cancer as well as other proliferative disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hua Zhong, Jun Yang, Bin Zhang, et al. 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