Pan-cancer analysis of Chromobox (CBX) genes for prognostic significance and cancer classification

Naqvi, Ahmad Abu Turab; Rizvi, Syed A.; Hassan, Md. Imtaiyaz

doi:10.1016/j.bbadis.2022.166561

Cited by 11 publications

(7 citation statements)

References 57 publications

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“…The pan-cancer analysis is a comprehensive and systematic approach to investigating and assessing the function and mechanism of a specific gene in tumorigenesis. Using the TCGA database, several genes were identified that may have a role in human cancers, such as FGL1 [30], CARM1 [31], CBX [32], LCK [33], and MNX1 [34]. In the present study, we conducted a systematic analysis of SKP2 expression across a variety of tumor forms, and the results revealed that practically most tumor types overexpressed SKP2 ).…”

Section: Discussionmentioning

confidence: 74%

Pan-Cancer Analysis of the Expression and Prognostic Value of S-Phase Kinase-Associated Protein 2

Nguyen

Hoang

Bui

2023

Open Access Maced J Med Sci

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BACKGROUND: S-Phase Kinase-Associated Protein 2 (SKP2) is essential in modulating metabolism processes, cell proliferation, and carcinogenesis DUE to its capacity to ubiquitinate and degrade various tumor-suppressive substrates. However, the actual biological and mechanism significance of SKP2 in the development of tumors and as a possible therapeutic target remains to be completely understood. AIM: This study aimed to explore the potential roles of the SKP2 gene in the oncologic pathogenesis of various cancers through an in-depth pan-cancer analysis including gene expression assessment, survival analysis, genetic alteration, and enrichment analysis. METHODS: Public databases including the Cancer Genome Atlas database, Genotype-Tissue Expression Project database, cBioPortal database, Gene Expression Profiling Interactive Analysis 2 database, Tumor Immune Estimation Resource version 2.0 database, and STRING database were used to detect the SKP2 expression, molecular mechanism, and its association with the prognosis across pan-cancer. RESULTS: SKP2 was significantly highly expressed in most types of cancers and was substantially correlated to the poor survival of patients with specific cancers based on the log-rank test. SKP2 had the highest frequency of alteration in lung cancer and amplification was the most common genetic alteration type. Finally, SKP2-related genes were identified and enrichment analyses were conducted. CONCLUSION: This study presented the first demonstration of the pan-cancer landscape of abnormal SKP2 expression, it could potentially serve as a predictive indicator and prospective therapeutic target.

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Section: Discussionmentioning

confidence: 74%

Pan-Cancer Analysis of the Expression and Prognostic Value of S-Phase Kinase-Associated Protein 2

Nguyen

Hoang

Bui

2023

Open Access Maced J Med Sci

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“…Recent studies have revealed the distinct Integrative Analysis of Genetic and Epigenetic Alterations in the CBX7 Gene Reveals Oncol Insights.2023;2:691 functions among CBX family members in cancer. For example, CBX3 was found to be upregulated, whereas CBX7 was downregulated in many types of human cancer [14][15][16][17][18][19][20][21][22]. Some studies have shown that CBX3 transcriptionally suppresses the p21 gene to promote cell proliferation [23][24][25], while CBX7 transcriptionally suppresses CCNE1 expression to inhibit cell proliferation [26].…”

Section: Introductionmentioning

confidence: 99%

“…These studies indicate that some CBX genes function as oncogenes and others act as tumor suppressor genes. Moreover, the expression of many CBX genes has a prognostic impact on human cancer [14][15][16][17][18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

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Integrative Analysis of Genetic and Epigenetic Alterations in the CBX7 Gene Reveals Its Tumor-Suppressive Function by Regulating the Cell Cycle in Human Breast Cancer

Cai¹,

Chang²,

Pérez-Losada³

et al. 2023

Oncol Insights

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CBX7 is a member of the chromobox gene family, which plays an important role in epigenetic transcriptional regulation. In this study, we found that compared to normal mammary tissues, mRNA levels of CBX7 are consistently significantly downregulated in breast cancers (BCs) across different datasets. Integrative multiomics analysis revealed the genetic and epigenetic mechanisms for the loss of CBX7 expression in BCs. Lower expression levels of CBX7 are significantly associated with shorter overall, disease-free, and distant metastasis-free survival of patients with BC. These prognostic impacts of CBX7 are independent of estrogen receptor status and PAM50 molecular subtypes. Coexpression analysis identified 207 genes consistently coexpressed with CBX7 (157 negatively and 50 positively). Gene Ontology, KEGG, and Reactome enrichment analysis revealed that cell cycle‑, DNA replication‑, and mitosis-related pathways are significantly overrepresented within the set of CBX7 negatively coexpressed genes, suggesting that CBX7 functions as a suppressor of the cell cycle. Moreover, transcription factor enrichment analysis detected the E2F family of transcription factors significantly associated with CBX7 negatively coexpressed genes, consistent with E2F function regulating the cell cycle. Furthermore, we found that loss of CBX7 expression significantly increases genomic instability and tumor mutation burden. Our findings indicate that CBX7 acts as a tumor suppressor in BC through its potential role in the negative regulation of cell proliferation and the maintenance of genome integrity.

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“… 4 – 6 Chromobox (CBX) family proteins are the core components of PRC1, which has been proved to be a transcription suppressor and play an important role in organ development and tumorigenesis. 7 , 8 There are eight members of CBX proteins family which can be further divided according to their molecular structures into HP1 group (formed by N-terminal and C-terminal chromodomains, contains CBX1, 3, 5) and Pc group (only n-terminal chromodomain, contains CBX2, 4, 6, 7, 8). 9 CBX proteins are involved in multiple types of tumor progression.…”

Section: Introductionmentioning

confidence: 99%

CBX4 deletion promotes tumorigenesis under KrasG12D background by inducing genomic instability

Chen,

Hou,

et al. 2023

Sig Transduct Target Ther

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Chromobox protein homolog 4 (CBX4) is a component of the Polycomb group (PcG) multiprotein Polycomb repressive complexes 1 (PRC1), which is participated in several processes including growth, senescence, immunity, and tissue repair. CBX4 has been shown to have diverse, even opposite functions in different types of tissue and malignancy in previous studies. In this study, we found that CBX4 deletion promoted lung adenocarcinoma (LUAD) proliferation and progression in KrasG12D mutated background. In vitro, over 50% Cbx4L/L, KrasG12D mouse embryonic fibroblasts (MEFs) underwent apoptosis in the initial period after Adeno-Cre virus treatment, while a small portion of survival cells got increased proliferation and transformation abilities, which we called selected Cbx4−/−, KrasG12D cells. Karyotype analysis and RNA-seq data revealed chromosome instability and genome changes in selected Cbx4−/−, KrasG12D cells compared with KrasG12D cells. Further study showed that P15, P16 and other apoptosis-related genes were upregulated in the primary Cbx4−/−, KrasG12D cells due to chromosome instability, which led to the large population of cell apoptosis. In addition, multiple pathways including Hippo pathway and basal cell cancer-related signatures were altered in selected Cbx4−/−, KrasG12D cells, ultimately leading to cancer. We also found that low expression of CBX4 in LUAD was associated with poorer prognosis under Kras mutation background from the human clinical data. To sum up, CBX4 deletion causes genomic instability to induce tumorigenesis under KrasG12D background. Our study demonstrates that CBX4 plays an emerging role in tumorigenesis, which is of great importance in guiding the clinical treatment of lung adenocarcinoma.

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Pan-cancer analysis of Chromobox (CBX) genes for prognostic significance and cancer classification

Cited by 11 publications

References 57 publications

Pan-Cancer Analysis of the Expression and Prognostic Value of S-Phase Kinase-Associated Protein 2

Pan-Cancer Analysis of the Expression and Prognostic Value of S-Phase Kinase-Associated Protein 2

Integrative Analysis of Genetic and Epigenetic Alterations in the CBX7 Gene Reveals Its Tumor-Suppressive Function by Regulating the Cell Cycle in Human Breast Cancer

CBX4 deletion promotes tumorigenesis under KrasG12D background by inducing genomic instability

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