研究动态
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BCL7B,一个SWI/SNF复合物亚单位,协调癌症免疫和干细胞特性。

BCL7B, a SWI/SNF complex subunit, orchestrates cancer immunity and stemness.

发表日期:2023 Aug 30
作者: Sayaka Higuchi, Yuji Suehiro, Luna Izuhara, Sawako Yoshina, Akira Hirasawa, Shohei Mitani
来源: Epigenetics & Chromatin

摘要:

癌症是人类死亡的主要原因之一。在这里,我们关注B细胞淋巴瘤7蛋白家族成员B (BCL7B)基因,该基因是SWI/SNF染色质重塑复合物的一个辅助亚单位。为了表征BCL7B的功能,我们利用CRISPR/Cas9基因组编辑系统生成了异质性的BCL7B缺失的胃癌细胞系。通过RNA-seq比较了父细胞与每个ΔBCL7B细胞系之间的全面基因表达模式。结果显示ΔBCL7B细胞系中免疫相关基因显著下调,干细胞相关基因上调。此外,通过H3K27me3抗体进行的ChIP-seq分析比较了父细胞与每个ΔBCL7B细胞系之间的表观遗传修饰序列的变化。经过机器学习,我们检测到了Centroid序列的变化,这对抗原呈递产生了影响。BCL7B在癌细胞中的调控导致了癌瘤干细胞样特征的获得和免疫逃避表型的获得。© 2023 BioMed Central Ltd., Springer Nature的一部分。
Cancer is one of the main causes of human death. Here, we focus on the B-cell lymphoma 7 protein family member B (BCL7B) gene, an accessory subunit of the SWI/SNF chromatin-remodelling complex. To characterize the function of BCL7B, heterozygous BCL7B-deficient stomach cancer cell lines were generated with the CRISPR/Cas9 genome editing system. The comprehensive gene expression patterns were compared between parental cells and each ΔBCL7B cell line by RNA-seq. The results showed marked downregulation of immune-related genes and upregulation of stemness-related genes in the ΔBCL7B cell lines. Moreover, by ChIP-seq analysis with H3K27me3 antibody, the changes of epigenetic modification sequences were compared between parental cells and each ΔBCL7B cell line. After machine learning, we detected the centroid sequence changes, which exerted an impact on antigen presentation. The regulation of BCL7B expression in cancer cells gives rise to cancer stem cell-like characteristics and the acquisition of an immune evasion phenotype.© 2023. BioMed Central Ltd., part of Springer Nature.