{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Colon cancer–associated transcript 2 (CCAT2) is an oncogenic long noncoding RNA that is frequently overexpressed in a variety of human malignancies—including colorectal, lung, esophageal, glioma, prostate, cervical, and triple‐negative breast cancers—and its high expression is consistently associated with tumor growth, invasion, metastasis, and poor clinical outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Mechanistically, CCAT2 has been shown to modulate critical oncogenic pathways. In colorectal and esophageal cancers, CCAT2 enhances WNT signaling and MYC transcription via interaction with transcription factors such as TCF7L2."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition, it impairs the maturation of microRNA‑145—thereby promoting cancer stem cell properties and epithelial–mesenchymal transition (EMT)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", while also upregulating adjacent oncogenes in prostate and triple‑negative breast cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n CCAT2 further influences cancer metabolism by binding the CFIm complex to regulate the alternative splicing of glutaminase, thereby favoring metabolic reprogramming in an allele‑specific manner."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Its role in promoting chromosomal instability has been linked to the stabilization of ribosomal biogenesis factors such as BOP1, which in turn activates aurora kinase B, contributing to genomic missegregation and chemoresistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, CCAT2 expression has been detected in the nucleus and circulation (often protected within exosomes), underscoring its potential as a noninvasive diagnostic and prognostic biomarker in cancers like colorectal carcinoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": " In non–small cell lung cancer, CCAT2 promotes tumorigenesis by modulating the Pokemon/p21 regulatory axis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": ", while in esophageal cancer, its high expression correlates with radioresistance through suppression of p53 and modulation of p70S6K1 signaling pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": " Finally, meta‑analysis data further support CCAT2 as a robust predictor of poor overall and progression‑free survival, as well as of metastatic propensity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies establish CCAT2 as a multifunctional oncogene that orchestrates diverse aspects of tumor progression—from transcriptional deregulation and altered RNA processing to metabolic reprogramming and genomic instability—making it a promising target for both prognostic biomarker development and therapeutic intervention."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}, {"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hui Ling, Riccardo Spizzo, Yaser Atlasi, et al. 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