Zheng Zong-Qing, Yuan Gui-Qiang, Kang Na-Ling, Nie Qian-Qian, Zhang Guo-Guo, Wang Zhong
Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.
Department of Neurosurgery, Changshu Second People's Hospital, Suzhou, China.
Front Neurol. 2022 Aug 11;13:912039. doi: 10.3389/fneur.2022.912039. eCollection 2022.
The chromobox family, a critical component of epigenetic regulators, participates in the tumorigenesis and progression of many malignancies. However, the roles of the CBX family members (CBXs) in glioblastoma (GBM) remain unclear.
The mRNA expression of CBXs was analyzed in tissues and cell lines by Oncomine and Cancer Cell Line Encyclopedia (CCLE). The differential expression of CBXs at the mRNA level was explored in The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases with the "beeswarm" R package. The protein expression of CBXs in GBM was further examined on Human Protein Atlas (HPA). The correlations between CBXs and IDH mutation and between CBXs and GBM subtypes were investigated in the TCGA portal and CGGA database with the "survminer" R package. The alteration of CBXs and their prognostic value were further determined the cBioPortal and CGGA database with the "survival" R package. The univariate and multivariate analyses were performed to screen out the independent prognostic roles of CBXs in the CGGA database. Cytoscape was used to visualize the functions and related pathways of CBXs in GBM. U251 and U87 glioma cells with gene intervention were used to validate the role of CBX7/8 in tumor proliferation and invasion. Proliferation/invasion-related markers were conducted by Western blot and immunostaining.
CBXs presented significantly differential expressions in pan-cancers. CBX2/3/5/8 were upregulated, whereas CBX6/7 were downregulated at mRNA level in GBM of TCGA and CGGA databases. Similarly, high expression of CBX2/3/5 and low expression of CBX6/8 were further confirmed at the protein level in the HPA. CBX2/6/7 were positively correlated with IDH mutation and CBX1/2/4/5/8 were closely related to GBM subtypes. CBX7 and CBX8 presented the independent prognostic factors for GBM patient survival. GO and KEGG analyses indicated that CBXs were closely related to the histone H3-K36, PcG protein complex, ATPase, and Wnt pathway. The overexpression of CBX7 and underexpression of CBX8 significantly inhibited the proliferation and invasion of glioma cells and .
Our results suggested that CBX7 and CBX8 served as independent prognostic indicators that promoted the proliferation and invasion of glioma cells, providing a promising strategy for diagnosing and treating GBM.
染色质盒家族作为表观遗传调控因子的关键组成部分，参与了多种恶性肿瘤的发生和发展。然而，染色质盒家族成员（CBXs）在胶质母细胞瘤（GBM）中的作用仍不清楚。
通过Oncomine和癌细胞系百科全书（CCLE）分析组织和细胞系中CBXs的mRNA表达。使用“beeswarm”R包在癌症基因组图谱（TCGA）和中国胶质瘤基因组图谱（CGGA）数据库中探索CBXs在mRNA水平的差异表达。在人类蛋白质图谱（HPA）上进一步检测GBM中CBXs的蛋白质表达。使用“survminer”R包在TCGA门户和CGGA数据库中研究CBXs与异柠檬酸脱氢酶（IDH）突变之间以及CBXs与GBM亚型之间的相关性。使用“survival”R包在cBioPortal和CGGA数据库中进一步确定CBXs的改变及其预后价值。进行单因素和多因素分析以筛选出CBXs在CGGA数据库中的独立预后作用。使用Cytoscape可视化CBXs在GBM中的功能和相关途径。使用基因干预的U251和U87胶质瘤细胞来验证CBX7/8在肿瘤增殖和侵袭中的作用。通过蛋白质印迹和免疫染色检测增殖/侵袭相关标志物。
CBXs在泛癌中呈现出显著的差异表达。在TCGA和CGGA数据库的GBM中，CBX2/3/5/8在mRNA水平上调，而CBX6/7下调。同样，在HPA中蛋白质水平进一步证实了CBX2/3/5的高表达和CBX6/8的低表达。CBX2/6/7与IDH突变呈正相关，CBX1/2/4/5/8与GBM亚型密切相关。CBX7和CBX8是GBM患者生存的独立预后因素。基因本体（GO）和京都基因与基因组百科全书（KEGG）分析表明，CBXs与组蛋白H3-K36、多梳蛋白复合体、ATP酶和Wnt信号通路密切相关。CBX7的过表达和CBX8的低表达显著抑制了胶质瘤细胞的增殖和侵袭。
我们的结果表明，CBX7和CBX8作为独立的预后指标，促进了胶质瘤细胞的增殖和侵袭，为GBM的诊断和治疗提供了一个有前景的策略。
