{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FOXR2 is emerging as a pivotal oncogenic transcription factor across a broad spectrum of human cancers. Its aberrant overexpression has been identified in non‐small cell lung cancer, hepatocellular carcinoma, colorectal cancer, prostate cancer, breast cancer, and several central nervous system tumors – including medulloblastoma and pineoblastoma – where elevated FOXR2 levels are consistently associated with enhanced cell proliferation, migration, invasion, and metastasis, as well as poor clinical prognosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Mechanistically, FOXR2 enhances tumor progression by directly interacting with and stabilizing MYC and its partners to boost MYC transcriptional activity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", and by modulating key oncogenic signaling cascades including the WNT/β‐catenin and Hedgehog pathways. These pathways lead to upregulation of cell cycle regulators such as cyclin D1 and c‐Myc, further promoting malignant cell growth and survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, FOXR2 function is intricately regulated at the post‐transcriptional level by noncoding RNAs. For example, circular RNAs such as circABCB10 and LINC00520 act as competing endogenous RNAs that sequester microRNAs (e.g., miR‐1252‐5p and miR‐532‐3p), thereby relieving their suppressive effect on FOXR2 expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_fs", "start_ref": "12", "end_ref": "14"}]}, {"type": "t", "text": " Moreover, FOXR2 activation has been shown to influence the permeability of the blood–brain barrier in glioma and to confer chemoresistance in bladder cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In central nervous system embryonal tumors, FOXR2 activation defines distinct subgroups—such as CNS neuroblastoma with FOXR2 activation and PB‐MYC/FOXR2 in pineoblastoma—that exhibit aggressive clinical behavior and could serve as potential diagnostic markers and therapeutic targets."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore the multifaceted role of FOXR2 in oncogenesis: by driving key signaling pathways and by being subject to regulation by noncoding RNAs, FOXR2 emerges as a promising molecular biomarker and a potential therapeutic target in several cancer types."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xufeng Tian, Lin Zhang, Yan Jiao, et al. 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