{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Multiple studies have demonstrated that the long non‐coding RNA (lncRNA) EWSAT1 plays an oncogenic role in several human tumors. In Ewing sarcoma, EWSAT1 is transcriptionally upregulated downstream of the pathognomonic EWS–FLI1 fusion protein and contributes to tumorigenesis by repressing gene expression programs essential for cell differentiation and by promoting proliferation and colony formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In nasopharyngeal carcinoma (NPC), elevated EWSAT1 levels are associated with poor survival, and mechanistic studies indicate that EWSAT1 acts as a competitive “sponge” for specific microRNA clusters (miR‐326/330‐5p), resulting in the upregulation of cyclin D1 and enhanced cell growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In osteosarcoma, functional assays have revealed that overexpression of EWSAT1 promotes proliferation, migration, and invasion. One study demonstrated that EWSAT1 exerts its oncogenic influence by positively regulating the transcription of another lncRNA, MEG3, while additional evidence shows that EWSAT1 sponges miR‐24‐3p to release the expression of ROCK1, which drives actin stress fiber formation and metastatic potential"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In colorectal cancer, increased EWSAT1 expression correlates with deeper invasion, lymph node metastasis, and advanced TNM stage. Knockdown experiments indicate that reducing EWSAT1 diminishes cell proliferation and invasion, partly through modulating epithelial–mesenchymal transition regulators."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Similarly, in cervical cancer and non‐small cell lung cancer (NSCLC), EWSAT1 is overexpressed and associated with poor prognosis. In cervical cancer, EWSAT1 functions as a competing endogenous RNA (ceRNA) by binding miR‐330‐5p to upregulate CPEB4, which in turn enhances cell proliferation, migration, and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In NSCLC, EWSAT1 also sponges miR‐330‐5p, thereby relieving the repression on ITGA5—a key mediator of cell adhesion and invasion—resulting in increased tumor cell growth and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In osteosarcoma patients, high EWSAT1 expression has been linked with advanced clinical stage, distant metastasis, poorer overall survival, and shorter disease‐free survival, underscoring its potential as an independent prognostic biomarker."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In ovarian cancer, upregulated EWSAT1 suppresses miR‐330‐5p levels, leading to increased expression of the target gene PDIA3. This axis promotes cell proliferation, colony formation, and invasion, further supporting the oncogenic role of EWSAT1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n A recent meta‐analysis across various cancer types has confirmed that high EWSAT1 expression is significantly associated with poor overall survival, increased metastasis, and advanced tumor stage, emphasizing its broad clinical relevance as a prognostic marker."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, in glioma, elevated EWSAT1 levels contribute to tumor progression through binding and suppressing microRNAs (e.g., miR‐152‐3p), thereby promoting cell proliferation and invasion. This reinforces the notion that EWSAT1 acts as a central node in ceRNA networks that drive oncogenesis in diverse tumor types"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", and natural compounds such as calycosin have been shown to inhibit tumor cell growth by downregulating EWSAT1 and its downstream pathways in NPC."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings reveal that EWSAT1 operates as an oncogenic lncRNA across multiple cancers by acting as a molecular sponge for specific microRNAs; this, in turn, leads to the upregulation of key target genes involved in cell cycle progression, epithelial–mesenchymal transition, cytoskeletal reorganization, and metastatic spread. Owing to its consistent association with aggressive tumor behavior and unfavorable clinical outcomes, EWSAT1 represents a promising biomarker and a potential therapeutic target for precision oncology.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Michelle Marques Howarth, David Simpson, Siu P Ngok, et al. 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