{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZNF382 is a Krüppel‐associated box (KRAB) zinc finger protein originally isolated from human heart tissue, where its early embryonic expression suggests roles in normal development and organogenesis ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "]. In normal tissues, ZNF382 is broadly expressed; however, in multiple carcinomas its expression is frequently suppressed through promoter CpG methylation, indicating a pivotal role as a tumor suppressor ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "].\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistic studies demonstrate that ZNF382 acts as a transcriptional repressor by directly binding to the promoters of various oncogenes and inhibiting key signaling pathways including NF‑κB, AP‑1, Wnt/β‑catenin, and NOTCH cascades. It downregulates oncogenic drivers such as MYC, MITF, HMGA2, CDK6, FOS, JUN, DVL2, and FZD1, often through heterochromatin-mediated silencing involving interactions with heterochromatin protein HP1. Furthermore, aberrant expression of MAGE family proteins can disrupt ZNF382 function by inducing its ubiquitination and degradation, thereby relieving repression of its target genes ["}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": "].\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, the epigenetic inactivation of ZNF382 via promoter hypermethylation is a common event in a variety of malignancies. Its silencing has been observed in pediatric acute myeloid leukemia, where decreased transcript levels correlate with minimal residual disease, as well as in HBV-related hepatocellular carcinoma and esophageal, gastric, and bladder cancers, where reduced expression is linked to enhanced tumorigenicity and poorer patient outcomes. Moreover, reviews of the literature underscore the potential of DNA hypomethylating agents to restore ZNF382 expression and its tumor-suppressive functions, highlighting the promise of reversing epigenetic silencing for therapeutic benefit ["}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "].\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kaimei Luo, Wuzhou Yuan, Chuanbin Zhu, et al. 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