{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The long noncoding RNA EMX2OS plays multifaceted, context‐dependent roles in both developmental processes and cancer. In the developing central nervous system, EMX2OS modulates the expression of its sense partner EMX2 by facilitating post‐transcriptional downregulation—possibly through a Dicer‐dependent mechanism—thereby establishing a reciprocal regulatory loop critical for proper CNS patterning."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In several cancers, EMX2OS exhibits divergent functions. In papillary thyroid cancer, reduced EMX2OS levels are strongly associated with adverse recurrence‐free survival, suggesting its utility as an independent prognostic biomarker."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Similarly, in gastric cancer, EMX2OS was identified as a key enhancer RNA whose decreased expression correlates with aggressive clinicopathologic features and poor survival outcomes, highlighting its potential as a prognostic indicator."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In pediatric renal malignancies, such as Wilms’ tumor, EMX2OS acts as a tumor suppressor by functioning as a microRNA sponge for miR‑654‑3p, which leads to diminished cell proliferation, migration, invasion, and overall tumor growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In contrast, in ovarian cancer, overexpression of EMX2OS confers oncogenic properties—it binds to miR‑654, thereby upregulating AKT3 and its downstream target PD‑L1, and ultimately promoting enhanced cell proliferation, invasion, and sphere formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, in prostate cancer, EMX2OS is downregulated; its restoration—together with the binding of the RNA‐binding protein FUS—activates the cGMP‑PKG pathway, leading to suppressed cell proliferation, migration, and invasion, with consequent attenuation of tumor growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Network analyses in laryngeal squamous cell carcinoma have also implicated EMX2OS as an integral component of competing endogenous RNA circuits, underscoring its potential as a biomarker in malignant settings."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies reveal that EMX2OS exerts critical regulatory functions by modulating gene expression through ceRNA mechanisms, influencing both organ development and tumorigenesis. Its context‐dependent roles—ranging from tumor suppressive to oncogenic—make it a promising candidate for prognostic assessment and as a therapeutic target across diverse biological systems.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Giulia Spigoni, Chiara Gedressi, Antonello Mallamaci "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of Emx2 expression by antisense transcripts in murine cortico-cerebral precursors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0008658"}], "href": "https://doi.org/10.1371/journal.pone.0008658"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20066053"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20066053"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yi Gu, Chao Feng, Tong Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The downregulation of lncRNA EMX2OS might independently predict shorter recurrence-free survival of classical papillary thyroid cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0209338"}], "href": "https://doi.org/10.1371/journal.pone.0209338"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30576338"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30576338"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ge-Xin Liu, Yu-Zhen Tan, Guo-Chao He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EMX2OS plays a prognosis-associated enhancer RNA role in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Medicine (Baltimore) (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MD.0000000000027535"}], "href": "https://doi.org/10.1097/MD.0000000000027535"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34731149"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34731149"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Zhi-Hong Chen, Ming-Yu Cui, Hong-Mei Zhang "}, {"type": "b", "children": [{"type": "t", "text": "EMX2OS Delays Wilms'Tumor Progression via Targeting miR-654-3p."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Clin Lab Sci (2022)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35181613"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35181613"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Meng Duan, Meixia Fang, Changhe Wang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "LncRNA EMX2OS, Regulated by TCF12, Interacts with FUS to Regulate the Proliferation, Migration and Invasion of Prostate Cancer Cells Through the cGMP-PKG Signaling Pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Onco Targets Ther (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2147/OTT.S243552"}], "href": "https://doi.org/10.2147/OTT.S243552"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32801740"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32801740"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Zhengyi Tang, Ganguan Wei, Longcheng Zhang, et al. 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