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ZNF433在癌症中的功能与机制：从转录调控到临床应用
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Abstract:
克鲁佩尔相关盒锌指蛋白(KRAB-ZFPs, Krüppel-Associated Box Zinc Finger Proteins)是人类基因组中数量最多的转录因子家族，广泛参与基因表达调控、生长发育及细胞信号通路的调节。锌指蛋白433 (ZNF433, Zinc Finger Protein 433)基因是KRAB-ZFPs家族的成员，其分子功能和在癌症中的作用尚未被充分研究。在前列腺癌中，ZNF433高表达可促进β-catenin/TCF复合物的形成，激活Wnt/β-catenin信号通路，进而促进癌细胞增殖和迁移，表现为促癌因子。而在肾透明细胞癌中，ZNF433表达下调，其低表达与更高级别的肿瘤分期及较差预后相关，可能与启动子区域的高甲基化导致的转录沉默有关，从而影响肿瘤的发生与进展，表现为抑癌因子。此外，ZNF433的异常表达与癌症患者的临床预后密切相关，提示其在癌症诊断和治疗中的潜在应用价值。本文综述了ZNF433的分子结构、生物学功能及其在前列腺癌和肾透明细胞癌中的作用机制，并探讨了其作为癌症生物标志物和治疗靶点的潜力。未来，进一步解析ZNF433的直接靶基因、上游调控机制及其与肿瘤微环境的相互作用，将有助于深入理解其在癌症中的功能，并为精准治疗提供新的策略。
Krüppel-Associated Box Zinc Finger Proteins (KRAB-ZFPs) are the largest family of transcription factors in the human genome, extensively involved in gene expression regulation, development, and modulation of cellular signaling pathways. Zinc Finger Protein 433 (ZNF433) is a member of the KRAB-ZFPs family, but its molecular function and role in cancer have not been fully elucidated. In prostate cancer, ZNF433 overexpression promotes the formation of the β-catenin/TCF complex, activating the Wnt/β-catenin signaling pathway, which subsequently enhances cancer cell proliferation and migration, functioning as an oncogene. In contrast, in clear cell renal cell carcinoma, ZNF433 expression is downregulated, and its low expression is associated with higher tumor grade, advanced stage, and poorer prognosis. This downregulation may be linked to promoter hypermethylation, leading to transcriptional silencing, thereby influencing tumorigenesis and progression, functioning as a tumor suppressor. Moreover, abnormal expression of ZNF433 is closely correlated with clinical prognosis in cancer patients, suggesting its potential application in cancer diagnosis and therapy. This review summarizes the molecular structure, biological functions, and roles of ZNF433 in prostate cancer and ccRCC, while also exploring its potential as a biomarker and therapeutic target for cancer. In the future, further elucidation of ZNF433’s direct target genes, upstream regulatory mechanisms, and interactions with the tumor microenvironment will help deepen our understanding of its role in cancer and provide new strategies for precision therapy.
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