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CHD 家族基因的分子特征和致癌作用:基于生物信息学和生物学分析的泛癌分析。

Molecular characteristics and oncogenic role of CHD family genes: a pan-cancer analysis based on bioinformatic and biological analysis.

机构信息

Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting, School of Life Sciences, Jiangsu Normal University, Xuzhou, Jiangsu, China.

出版信息

Sci Rep. 2024 Aug 15;14(1):18923. doi: 10.1038/s41598-024-68644-9.

Abstract

Chromodomain helicase DNA-binding protein (CHD) gene family, an ATP (adenosine triphosphate) -dependent chromatin remodeler family, is involved in multiple developmental process and tumor development. However, there have been none pan-cancer analyses of this family. The expression levels, survival profiles, mutation profiles and immune infiltration of the CHD family genes from TCGA and TARGET database were analyzed using online tools or R packages. Interestingly, all types of CHD gene expressions were associated with the prognosis of Neuroblastoma, Acute lymphoblastic leukemia-Phase 3 and Acute Myeloid Leukemia (All P < 0.05). Knock down of CHD7 and CHD9 in K562 (human erythromyeloblastoid leukemia) and HEC-1-B (human endometrial adenocarcinoma) cells significantly inhibit cell proliferation and migration (P < 0.05). Proliferation, colony formation and migration assays were performed in CHD7 and CHD9 knockdown K562 and HBC-1-B cell lines. Mechanisms were also analyzed by PPI and GO ontology for our experiments. Histone modification, especially the methylation of H3K4, might be involved in CHD7 and CHD9 related oncogenesis. Through bioinformatic analysis, we showed CHD genes significantly affected the prognosis of different tumor types, including childhood tumor. Our findings provide new insights into the function and mechanism of CHD gene family, especially in CHD7 and CHD9.

摘要

染色质解旋酶 DNA 结合蛋白(CHD)基因家族是一种 ATP(三磷酸腺苷)依赖性染色质重塑家族,参与多种发育过程和肿瘤发生。然而,目前尚无针对该家族的泛癌分析。本研究利用在线工具或 R 包分析了 TCGA 和 TARGET 数据库中 CHD 家族基因的表达水平、生存曲线、突变谱和免疫浸润情况。有趣的是,所有类型的 CHD 基因表达均与神经母细胞瘤、急性淋巴细胞白血病-3 期和急性髓系白血病的预后相关(均 P<0.05)。在 K562(人红白血病母细胞)和 HEC-1-B(人子宫内膜腺癌)细胞中敲低 CHD7 和 CHD9 可显著抑制细胞增殖和迁移(P<0.05)。在敲低 CHD7 和 CHD9 的 K562 和 HBC-1-B 细胞系中进行增殖、集落形成和迁移实验。通过蛋白质-蛋白质相互作用(PPI)和基因本体论(GO)对我们的实验进行了机制分析。组蛋白修饰,特别是 H3K4 的甲基化,可能参与了 CHD7 和 CHD9 相关的肿瘤发生。通过生物信息学分析,我们表明 CHD 基因显著影响不同肿瘤类型的预后,包括儿童肿瘤。我们的研究结果为 CHD 基因家族的功能和机制提供了新的见解,特别是在 CHD7 和 CHD9 方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcff/11324730/717cc0aeb2fe/41598_2024_68644_Fig1_HTML.jpg

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