乳腺癌是全球最常见的肿瘤类型之一。乳腺癌中经常检测到染色体 8q24 的拷贝数扩增。 ZNF623 是一个相对未被探索的基因，定位于 8q24。在这里，我们探讨了 ZNF623 在乳腺癌发生中的表达谱、预后意义和生物学作用。为了评估 ZNF623 在不同癌症类型中的 mRNA 表达模式和预后相关性，我们进行了生物信息学分析。使用 ZNF623 shRNA/siRNA 抑制该基因的表达，并通过用含有 ZNF623 cDNA 的质粒转染来增强该基因的表达。采用细胞活力测定、克隆形成测定和transwell迁移测定来评估乳腺癌细胞系的增殖、活力和侵袭能力。荧光素酶报告基因检测是确定 ZNF623 转录活性的关键工具。采用 IP-MS 和 co-IP 验证 ZNF623 与 CtBP1 相互作用。进行 ChIP 分析和 ChIP-qPCR 来评估 ZNF623/CtBP1 复合物靶向的基因。采用流式细胞术评估 p65 的磷酸化状态。ZNF623 表达在乳腺癌 (BC) 中显着升高。预后分析表明，ZNF623 表达越高，表明生存期越差。功能实验发现，ZNF623 的上调显着增强了乳腺癌细胞的增殖和迁移能力。荧光素酶报告基因检测表明 ZNF623 是一种转录抑制因子。免疫沉淀偶联质谱分析揭示了相互作用组中 ZNF623 和 CtBP1 之间的物理关联。 ChIP-seq 和 TCGA DEG 分析的联合分析表明，ZNF623/CtBP1 复合物抑制了一系列基因，例如 NF-kappaB 信号通路的负调控。流式细胞术分析发现ZNF623的敲低降低了p65的磷酸化水平，表明ZNF623可以调节NF-κB通路的活性。ZNF623预测BC的不良预后并促进乳腺癌的生长和转移。通过招募 CtBP1，ZNF623 可以从转录水平抑制 NF-κB 抑制剂（包括 COMMD1、NFKBIL1、PYCARD 和 BRMS1）的表达。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Breast cancer ranks among the most prevalent tumor types worldwide. Copy number amplification of chromosome 8q24 is frequently detected in breast cancer. ZNF623 is a relatively unexplored gene mapped to 8q24. Here, we explore the expression profile, prognostic significance, and biological action of ZNF623 in breast carcinogenesis.To evaluate the mRNA expression pattern and prognostic relevance of ZNF623 across different cancer types, we conducted bioinformatic analyses. The expression of the gene was suppressed using ZNF623 shRNAs/siRNAs and augmented through transfection with plasmids containing ZNF623 cDNA. Cell viability assay, clonogenic assay, and transwell migration assay were utilized to assess the proliferation, viability, and invasion capacity of breast cancer cell lines. Luciferase reporter assay served as a pivotal tool to ascertain the transcriptional activity of ZNF623. IP-MS and co-IP were employed to validate that ZNF623 interacted with CtBP1. ChIP analysis and ChIP-qPCR were conducted to assess the genes targeted by ZNF623/CtBP1 complex. Flow cytometry was conducted to evaluate the phosphorylation status of p65.ZNF623 expression was notably elevated in breast cancer (BC). Prognostic analysis indicated higher expression of ZNF623 indicated worse survival. Functional experiments discovered that the upregulation of ZNF623 significantly enhanced both the proliferative and migratory capacities of breast cancer cells. Luciferase reporter assay indicated that ZNF623 was a transcription repressor. Immunoprecipitation coupled mass spectrometry analysis revealed a physical association between ZNF623 and CtBP1 in the interaction group. The conjoint analysis of ChIP-seq and TCGA DEG analysis revealed that the ZNF623/CtBP1 complex repressed a series of genes, such as negative regulation of the NF-kappaB signaling pathway. Flow cytometry analysis discovered that knockdown of ZNF623 decreased the phosphorylation level of p65, indicating that ZNF623 could regulate the activity of the NF-κB pathway.ZNF623 predicts poor prognosis of BC and enhances breast cancer growth and metastasis. By recruiting CtBP1, ZNF623 could suppress NF-κB inhibitors, including COMMD1, NFKBIL1, PYCARD, and BRMS1, expression from the transcription level.Copyright © 2024 Elsevier Inc. All rights reserved.