CBX Family Members in Two Major Subtypes of Renal Cell Carcinoma: A Comparative Bioinformatic Analysis

Grimaldi, Anna; Affinito, Ornella; Salvatore, Marco; Franzese, Monica

doi:10.3390/diagnostics12102452

Cited by 6 publications

(7 citation statements)

References 74 publications

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“…Initially, we discovered that CBX3 was substantially expressed in renal carcinoma, concerning a dismal prognosis—especially in high-grade (T3 + T4) ccRCC; these findings agreed with those of earlier research [ 31 ]. The analysis of the CCLE datasets revealed that CBX3 was substantially expressed in kidney cancer cell lines.…”

Section: Discussionsupporting

confidence: 90%

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

Chen,

Lin,

zheng

et al. 2023

J Transl Med

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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.

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Section: Discussionsupporting

confidence: 90%

“…However, research on the link between CBX3 and ccRCC is minimal. Previous research has demonstrated that CBX3 is an oncogene associated with poor outcomes in ccRCC; however, the function and potential mechanism of CBX3 remain unclear [ 31 ]. Therefore, we investigated the role of CBX3 in ccRCC.…”

Section: Discussionmentioning

confidence: 99%

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

Chen,

Lin,

zheng

et al. 2023

J Transl Med

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“…The overexpression of HP1γ in pancreatic DAC promotes cell cycle transition-associated tumor progression [ 70 ]. HP1γ expression is higher in tumor tissues than paired normal tissues in kidney cancer [ 71 ], CRC [ 69 ], gastric cancer [ 72 ], and non-small cell lung cancer [ 73 ]. These unfavorable roles of HP1γ might be caused by its transcriptional activator function [ 74 , 75 ] collaborating with nuclear moonlighting metalloproteinases (MMP) [ 39 , 40 , 76 ] or RNA processing [ 77 ].…”

Section: Discussionmentioning

confidence: 99%

SCAND1 Reverses Epithelial-to-Mesenchymal Transition (EMT) and Suppresses Prostate Cancer Growth and Migration

Eguchi

Csizmadia

Kawai

et al. 2022

Cells

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Epithelial–mesenchymal transition (EMT) is a reversible cellular program that transiently places epithelial (E) cells into pseudo-mesenchymal (M) cell states. The malignant progression and resistance of many carcinomas depend on EMT activation, partial EMT, or hybrid E/M status in neoplastic cells. EMT is activated by tumor microenvironmental TGFβ signal and EMT-inducing transcription factors, such as ZEB1/2, in tumor cells. However, reverse EMT factors are less studied. We demonstrate that prostate epithelial transcription factor SCAND1 can reverse the cancer cell mesenchymal and hybrid E/M phenotypes to a more epithelial, less invasive status and inhibit their proliferation and migration in DU-145 prostate cancer cells. SCAND1 is a SCAN domain-containing protein and hetero-oligomerizes with SCAN-zinc finger transcription factors, such as MZF1, for accessing DNA and the transcriptional co-repression of target genes. We found that SCAND1 expression correlated with maintaining epithelial features, whereas the loss of SCAND1 was associated with mesenchymal phenotypes of tumor cells. SCAND1 and MZF1 were mutually inducible and coordinately included in chromatin with hetero-chromatin protein HP1γ. The overexpression of SCAND1 reversed hybrid E/M status into an epithelial phenotype with E-cadherin and β-catenin relocation. Consistently, the co-expression analysis in TCGA PanCancer Atlas revealed that SCAND1 and MZF1 expression was negatively correlated with EMT driver genes, including CTNNB1, ZEB1, ZEB2 and TGFBRs, in prostate adenocarcinoma specimens. In addition, SCAND1 overexpression suppressed tumor cell proliferation by reducing the MAP3K-MEK-ERK signaling pathway. Of note, in a mouse tumor xenograft model, SCAND1 overexpression significantly reduced Ki-67(+) and Vimentin(+) tumor cells and inhibited migration and lymph node metastasis of prostate cancer. Kaplan–Meier analysis showed high expression of SCAND1 and MZF1 to correlate with better prognoses in pancreatic cancer and head and neck cancers, although with poorer prognosis in kidney cancer. Overall, these data suggest that SCAND1 induces expression and coordinated heterochromatin-binding of MZF1 to reverse the hybrid E/M status into an epithelial phenotype and, inhibits tumor cell proliferation, migration, and metastasis, potentially by repressing the gene expression of EMT drivers and the MAP3K-MEK-ERK signaling pathway.

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“…The incidence and course of KIRC, a malignant neoplasm that has been demonstrated to be highly immunogenic, are closely correlated with the tumor microenvironment (TME) [28,29] . Fortunately, a close correlation is possible among CBX3 expression and the degree of immunocyte in ltration in KIRC [25,30] . The precise effects of CBX3 on the TME in KIRC remain unknown.…”

Section: Discussionmentioning

confidence: 95%

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

Chen

Lin

Zheng

et al. 2023

Preprint

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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 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 epithelial-to-mesenchymal transition (EMT) in vitro along with in vivo. Moreover, we provide distinct mechanistic evidence that CBX3 achieves all 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 CBX3 is overexpressed and promotes ccRCC advancement through PI3K/AKT activation and even immunological dysregulation, making it a potentially viable and beneficial target.

show abstract

CBX Family Members in Two Major Subtypes of Renal Cell Carcinoma: A Comparative Bioinformatic Analysis

Cited by 6 publications

References 74 publications

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

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

SCAND1 Reverses Epithelial-to-Mesenchymal Transition (EMT) and Suppresses Prostate Cancer Growth and Migration

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

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