CBX3 promotes clear cell renal carcinoma through PI3K/AKT activation and aberrant immunity

Background 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. Methods The Cancer Genome Atlas database served to evaluate CB...

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Bibliographic Details
Published in:Journal of translational medicine 2023-09, Vol.21 (1), p.1-600, Article 600
Main Authors: Chen, Jiasheng, Lin, Yuxin, zheng, Shukai, Chen, Qingshan, Tang, Shijie, Zhong, Xiaoping
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
AKT protein
Analysis
Antibodies
Biomarkers
Biotechnology
Cancer
Carcinoma
Carcinoma, Renal cell
Care and treatment
CBX3
Cell adhesion & migration
Cell division
Cell migration
Clear cell renal cell carcinoma
Clear cell-type renal cell carcinoma
Datasets
Development and progression
Gene expression
Gene set enrichment analysis
Genes
Genetic aspects
Genomes
Genomics
Health aspects
Immunity
Immunohistochemistry
Immunologic disorder
Kidney cancer
Laboratory animals
Medical prognosis
Medical research
Patients
PI3K/AKT signaling pathway
Pore size
Progression
Proteins
Stem cells
Survival analysis
Therapeutic targets
Western blotting
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Summary:Background 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. Methods 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. Results 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. Conclusions 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. Keywords: Clear cell renal cell carcinoma, CBX3, Progression, PI3K/AKT signaling pathway, Immunologic disorder
ISSN:1479-5876
1479-5876
DOI:10.1186/s12967-023-04478-9