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In addition, aberrant SHOX2 methylation has been linked to disease progression in non‐small‐cell lung cancer and has shown promise in the screening and staging of colorectal, biliary tract, and other cancers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its oncological applications, SHOX2 serves as a critical transcription factor during embryonic development. It is indispensable for the formation and proper function of the cardiac conduction system, including the sinoatrial node and pacemaking tissue, acting in part through the direct transcriptional activation of key targets such as BMP4. SHOX2 also contributes to limb and skeletal development by influencing chondrocyte maturation and hypertrophic differentiation, and its dysregulation has been implicated in congenital conditions such as familial atrial fibrillation. These developmental roles highlight the gene’s fundamental importance in organogenesis and structural patterning."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "22", "end_ref": "29"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, SHOX2 has emerged as an oncogenic driver that modulates epithelial-to-mesenchymal transition (EMT) and promotes tumor aggressiveness. Functional studies in breast, esophageal, bladder, and gastric cancers demonstrate that aberrant SHOX2 expression—often governed by microRNA-mediated regulation—can enhance cellular invasiveness, proliferation, and stemness by activating signaling pathways such as TGF-β and Wnt/β-catenin. 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