{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZIC5 is a member of the zinc‐finger of the cerebellum (ZIC) transcription factor family that plays crucial roles in normal animal development. It is implicated in neural patterning and the proliferation and differentiation of progenitor cells, with developmental studies suggesting that aberrations involving ZIC5 (together with other ZIC family members such as ZIC2) may contribute to brain malformations such as Dandy–Walker malformation. In this context, its normal expression is essential for proper meningeal progenitor cell function and early central nervous system development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn various cancer types, ZIC5 has been identified as an oncogenic factor. For instance, in glioma, up‐regulation of ZIC5 occurs via a circular RNA/miR-761 regulatory loop that enhances cellular proliferation and migration. In non-small cell lung cancer, ZIC5 functions as a potential novel oncogene. Similar oncogenic roles have been documented in melanoma, prostate cancer, and colorectal cancer, where its elevated expression promotes aggressiveness by transcriptionally up-regulating genes such as platelet-derived growth factor D (PDGFD) and by sustaining pathways involving focal adhesion kinase (FAK) and STAT3. In hepatocellular carcinoma, ZIC5 overexpression correlates with poor prognosis and facilitates the nuclear translocation of β-catenin along with Cyclin D1 expression, thereby promoting tumor invasion and metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional mechanistic studies further underscore the multifaceted role of ZIC5 in tumor biology. In colorectal cancer, for example, knockout of Zic5 leads to an altered glycolytic state, indicating that it plays a critical role in regulating glucose metabolism through the Wnt/β-catenin signaling axis. In nasopharyngeal carcinoma, ZIC5 operates within a miR-101-3p/SOX2 regulatory circuit that modulates cisplatin resistance, while emerging evidence also points to its involvement in cervical squamous cell carcinoma pathology. Such findings highlight ZIC5 not only as a key regulator of tumor cell proliferation, migration, and survival but also as a promising prognostic marker and therapeutic target across a range of malignant conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jun Aruga, Yayoi Nozaki, Minoru Hatayama, et al. 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