{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The long noncoding RNA "}, {"type": "b", "children": [{"type": "t", "text": "CCAT1"}]}, {"type": "t", "text": " has emerged as a multifunctional oncogene whose abnormal overexpression is observed in a variety of cancers. In colorectal cancer, a long‐isoform designated CCAT1‑L is transcribed from a super‐enhancer region upstream of MYC, where it promotes long‐range chromatin interactions through binding with architectural proteins such as CTCF, thereby enhancing MYC transcription."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In gallbladder cancer, CCAT1 functions as a competing endogenous RNA (ceRNA) that “sponges” miR‑218‑5p to de‐repress BMI1 expression, contributing to increased proliferation and invasiveness."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In colorectal tumors, high expression of CCAT1 from a super‐enhancer has also been linked to BET inhibitor sensitivity, underscoring its potential as a prognostic biomarker and therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In acute myeloid leukemia, CCAT1 promotes cell growth and represses monocytic differentiation by sequestering tumor–suppressive miR‑155, which leads to upregulation of oncogenic factors including MYC."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In glioma, CCAT1 is overexpressed and acts as a ceRNA for miR‑181b, thereby lifting repression on targets such as FGFR3 and PDGFRα to enhance cell proliferation, migration, and epithelial–mesenchymal transition (EMT)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Similarly, in intrahepatic cholangiocarcinoma, elevated CCAT1 levels facilitate migration and EMT by sponging miR‑152."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n CCAT1 upregulation is also notable in castration–resistant prostate cancer, where its high expression correlates with increased mortality."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In esophageal squamous cell carcinoma, CCAT1 enhances chemoresistance to cisplatin by targeting miR‑143 and modulating downstream effectors such as PLK1 and BUBR1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", while in gastric cancer it regulates cell migration by interacting with miR‑490 to control hnRNPA1 expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Finally, pan–cancer analyses further support an oncogenic role for CCAT1, highlighting its consistent overexpression and association with poor clinical outcome across multiple tumor types."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, these findings indicate that CCAT1 exerts its oncogenic effects through dual mechanisms: first, by modulating chromatin architecture and transcription of key oncogenes such as MYC, and second, by functioning as a ceRNA that sequesters specific microRNAs, thereby de–repressing multiple oncogenic pathways. These multifaceted roles not only contribute to enhanced proliferation, invasion, metastasis, and chemoresistance but also nominate CCAT1 as a potential biomarker and target for therapeutic intervention.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jian-Feng Xiang, Qing-Fei Yin, Tian Chen, et al. 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