CBX3 通过 PI3K/AKT 激活和异常免疫促进明显细胞肾癌的发展。
CBX3 promotes clear cell renal carcinoma through PI3K/AKT activation and aberrant immunity.
发表日期:2023 Sep 06
作者:
Jiasheng Chen, Yuxin Lin, Shukai Zheng, Qingshan Chen, Shijie Tang, Xiaoping Zhong
来源:
Journal of Translational Medicine
摘要:
染色体盒同源基因3(CBX3)在各种癌症中升高,并且显著促进着恶性行为的发生;尽管如此,它在透明细胞肾癌(ccRCC)中的确切参与仍然不明确。肿瘤基因组图谱数据库用于评估ccRCC患者中CBX3的产生和其与生存之间的关系。我们的团队使用体外和体内模型评估了CCBX3水平敲低对ccRCC细胞群体的影响。通过使用西方印迹和免疫组织化学分析方法,测定ccRCC细胞中的CBX3、与死亡相关的蛋白以及上皮间质转化(EMT)相关的蛋白。通过分析京都基因和基因组百科全书(KEGG)和基因本体(GO)以及基因集富集分析(GSEA),明确了与CBX3表达相关的生物过程和信号途径。使用各种在线工具评估了CBX3抑制的免疫相关活动。基因组和蛋白表达均显示CBX3在ccRCC中上调。进一步的功能分析揭示了CBX3在体外和体内增强细胞生长、迁移和EMT方面扮演重要角色。此外,研究结果提供了清楚的机械证据,证明CBX3通过激活PI3K/AKT通路在ccRCC中发挥其病理功能。最后,免疫检测显示CBX3与ccRCC的免疫关联显著。我们的结果表明,CBX3的过度表达通过PI3K/AKT的激活促进了ccRCC的进展,甚至导致免疫调节失调,使其成为潜在的、有益的治疗靶点。© 2023. BioMed Central有限公司,施普林格自然出版集团的一部分。
A chromobox homologue 3 (CBX3) is elevated in various cancers and significantly contributes to the promotion of malignant behavior; despite this, its exact involvement in clear cell renal cell carcinoma (ccRCC) is yet unknown.The Cancer Genome Atlas database served to evaluate CBX3 production and its connection to survival in patients with ccRCC. Our team evaluated the effects of knockdown of CBX3 levels in ccRCC cell populations using in vitro together with in vivo models. CBX3, proteins related to death, and epithelial-to-mesenchymal transition (EMT)-related proteins were measured in ccRCC cells using western blotting and immunohistochemical assays. Through the analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) and GeneOntology (GO) and Gene Set Enrichment Analysis (GSEA), the biological processes and signal pathways related to CBX3 expression were identified. Immune-related activity reduced by CBX3 was assessed using various online tools.Both genomic and protein expression showed that CBX3 was upregulated in ccRCC. Further functional analyses revealed that CBX3 played a crucial role in enhancing cell growth, migration, and EMT in vitro along with in vivo. Moreover, the study results provided distinct mechanistic evidence that CBX3 exerts its pathological functions in ccRCC by activating the PI3K/AKT pathway. Finally, immunoassays revealed that CBX3, a possible biomarker of ccRCC, was significantly associated with immunity.Our results suggest that the overexpression of CBX3 promotes ccRCC advancement through PI3K/AKT activation and even immunological dysregulation, making it a potentially viable and beneficial therapeutic target.© 2023. BioMed Central Ltd., part of Springer Nature.