关键词: CHD gene family Childhood tumor Epigenome Knock down Pan-cancer

Mesh : Humans Computational Biology / methods DNA Helicases / genetics metabolism DNA-Binding Proteins / genetics metabolism Neoplasms / genetics pathology Cell Proliferation / genetics Gene Expression Regulation, Neoplastic Cell Movement / genetics Prognosis Cell Line, Tumor Mutation

来  源:   DOI:10.1038/s41598-024-68644-9   PDF(Pubmed)

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:
染色体域解旋酶DNA结合蛋白(CHD)基因家族,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的发展。然而,没有对这个家族的泛癌症分析。表达水平,生存概况,使用在线工具或R包分析TCGA和TARGET数据库中CHD家族基因的突变谱和免疫浸润。有趣的是,所有类型的CHD基因表达均与神经母细胞瘤的预后相关,急性淋巴细胞白血病-3期和急性髓系白血病(均P<0.05)。敲低CHD7和CHD9对K562(人红粒细胞白血病)和HEC-1-B(人子宫内膜腺癌)细胞的增殖和迁移有明显抑制作用(P<0.05)。扩散,在CHD7和CHD9敲低K562和HBC-1-B细胞系中进行集落形成和迁移测定。我们的实验还通过PPI和GO本体分析了机制。组蛋白修改,尤其是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,我们发现CHD基因显著影响不同类型肿瘤的预后,包括儿童肿瘤.我们的发现为CHD基因家族的功能和机制提供了新的见解,尤其是CHD7和CHD9。
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