{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZEB2, also known as SIP1, is a pivotal transcriptional repressor that directly binds conserved E‐box elements in the promoter of E‐cadherin to silence its expression. In doing so, it enables epithelial‐to‐mesenchymal transition (EMT), a process central to tissue remodeling and tumor metastasis. The loss or downregulation of microRNAs—most notably members of the miR‑200 family—relieves this repression, thereby permitting ZEB2 upregulation and consequent EMT activation in diverse carcinomas."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn various tumor types—including pancreatic, hepatocellular, nasopharyngeal, bladder, gastric, and non‐small cell lung cancers—ZEB2 upregulation, often controlled by interactions with long non‐coding RNAs (such as MALAT1, TUG1, and XIST) and influenced by epigenetic modifications, is closely associated with enhanced cellular invasiveness, migration, and poor clinical outcome. Moreover, regulation of ZEB2 by other microRNAs (for example, miR‑145 and continued responsiveness to the miR‑200 family) highlights its function as a molecular switch that integrates extracellular signals to modulate cell cycle regulators and maintain EMT‐associated gene expression programs during cancer progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its oncogenic functions, ZEB2 plays a critical role during development. Its essential contribution to cortical interneuron differentiation underscores its importance in neuronal migration and proper cell‐fate determination. Moreover, haploinsufficiency of ZEB2 is the etiological basis of Mowat–Wilson syndrome—a congenital disorder characterized by distinct facial features, intellectual disability, and multiple malformations. Finally, post‐translational modifications such as sumoylation further fine‐tune ZEB2’s activity, allowing it to integrate cues from signaling pathways including transforming growth factor‑β, Notch, and p53 in order to regulate cell proliferation, apoptosis, and differentiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "J Comijn, G Berx, P Vermassen, et al. 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