{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZNF263 is a multifaceted C2H2 zinc finger transcription factor characterized by nine zinc finger domains along with KRAB and SCAN modules. Genome‐wide binding studies in human K562 cells revealed that ZNF263 occupies a specific 24‐nucleotide DNA motif—often located within transcribed gene regions—and can act as either an activator or repressor of transcription, depending on the context."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistically, ZNF263 modulates gene expression through diverse epigenetic and transcriptional regulatory mechanisms. For example, in glioblastoma, activation of the epidermal growth factor receptor (EGFR) via the MAPK pathway triggers ERK-mediated binding that stabilizes ZNF263; the stabilized protein then binds to the SIX3 promoter and recruits the KAP1/HATS/DNMT co‐repressor complex to induce histone modifications and DNA methylation, leading to transcriptional silencing."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Similarly, analysis of heparin biosynthetic gene promoters revealed a ZNF263 binding motif, and functional studies demonstrated that ZNF263 normally represses the expression of key glucosaminyl 3‐O-sulfotransferases (HS3ST1 and HS3ST3A1), thereby modulating heparan sulfate modifications critical to anticoagulant activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In hepatocellular carcinoma, aberrantly elevated O-GlcNAc transferase (OGT) activity modifies ZNF263 (notably at Ser662), promoting its chromatin association and facilitating activation of transcriptional networks that drive malignancy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In addition, studies in non-small cell lung cancer (NSCLC) have suggested that ZNF263 contributes to the regulation of interleukin-33 (IL33), apoptosis, and autophagy"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", while its ability to recruit DNMT1 to the EGFR promoter leads to DNA hypermethylation and repression of EGFR transcription—a mechanism that enhances responsiveness to tyrosine kinase inhibitors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn cancer contexts, the activities of ZNF263 have profound pathological implications. In renal cell carcinoma, ZNF263 has been shown to induce the expression of circFOXP1, which functions as a competing endogenous RNA to sequester miR-423-5p and upregulate U2AF2, promoting tumor cell proliferation, migration, invasion, and metabolic reprogramming."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In colorectal cancer, high ZNF263 expression is associated with advanced tumor grade, lymph node involvement, and distant metastasis; mechanistic studies revealed that ZNF263 directly binds to the STAT3 promoter to enhance its transcription and stabilize its mRNA, thereby facilitating epithelial–mesenchymal transition and contributing to chemoradiotherapy resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Collectively, these findings underscore the diverse and context-dependent roles of ZNF263 in transcriptional regulation, epigenetic modification, and oncogenic progression, making it a promising target for therapeutic intervention.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Seth Frietze, Xun Lan, Victor X Jin, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Zinc finger protein 263 upregulates interleukin 33 and suppresses autophagy to accelerate the malignant progression of non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Transl Oncol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12094-023-03325-z"}], "href": "https://doi.org/10.1007/s12094-023-03325-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37821764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37821764"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jiaqi Liang, Guoshu Bi, Qihai Sui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcription factor ZNF263 enhances EGFR-targeted therapeutic response and reduces residual disease in lung adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2024.113771"}], "href": "https://doi.org/10.1016/j.celrep.2024.113771"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38335093"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38335093"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Li Fang, Ting Ye, Yanmei An "}, {"type": "b", "children": [{"type": "t", "text": "Circular RNA FOXP1 Induced by ZNF263 Upregulates U2AF2 Expression to Accelerate Renal Cell Carcinoma Tumorigenesis and Warburg Effect through Sponging miR-423-5p."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2021/8050993"}], "href": "https://doi.org/10.1155/2021/8050993"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34514002"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34514002"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yadan Du, Yawen Chen, Zaihua Yan, et al. 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