{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRUNX3 plays a crucial role in immune regulation by contributing to T‐cell lineage commitment and function. It is essential for proper thymic T‐cell selection and the differentiation of T helper type 1 cells, acting in concert with key regulators such as T‐bet to promote interferon‑γ expression while repressing interleukin‑4. In addition, RUNX3 is induced by transforming growth factor‑β to facilitate the generation and function of inducible regulatory T cells via cooperation with other RUNX family members and FOXP3 activation, and its appropriate expression is required for the silencing of CD4 during cytotoxic T‑cell development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn a wide range of epithelial cancers—including those of the stomach, colon, breast, lung, and liver—RUNX3 acts as a tumor suppressor. Loss of its function, through mechanisms such as promoter hypermethylation, genetic deletion, or mislocalization from the nucleus to the cytoplasm, correlates with early neoplastic transformation and a poor prognosis. Such inactivation of RUNX3 disrupts key tumor‐suppressive signaling pathways including TGF‑β–mediated cell cycle arrest and the attenuation of oncogenic Wnt/β‑catenin activity. Furthermore, infections (for example, Helicobacter pylori) and related inflammatory processes have been found to trigger RUNX3 inactivation, suggesting its potential as an early diagnostic marker in premalignant lesions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the mechanistic level, RUNX3 activity is finely tuned by a variety of posttranslational and epigenetic regulatory events. 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