microRNA‐377 acts as a suppressor in esophageal squamous cell carcinoma through CBX3‐dependent P53/P21 pathway

He, Zhi‐Sheng; Chen, Junjing; Chen, Xiaoliang; Wang, Huanyuan; Tang, Lang; Han, Cheng

doi:10.1002/jcp.29631

Cited by 15 publications

(9 citation statements)

References 39 publications

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“…11 CBX3 is normally not detected in differentiated cells of various normal human tissues, but is detected in tumor tissues of various cancers, including esophageal, lung, cervical, colon, and breast cancers. [12][13][14][15] Substantial evidence indicates that CBX3 has cancerogenic and prognostic roles in various cancer types. However, the exact functions of CBX3 in HNSCC remain unclear.…”

Section: Discussionmentioning

confidence: 99%

CBX3 is a Prognostic Biomarker Correlated with ATR Activation and Immune Infiltration in Head and Neck Squamous Cell Carcinoma

Zhang¹,

Zhou²,

Liu³

2022

IJGM

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Background: Chromobox protein homolog (CBX) family members play important roles in the progression and prognosis of many cancers. However, their functional role in head and neck squamous cell carcinoma (HNSCC) remains largely unknown. Methods: In this study, we analyzed the expression and functions of CBX family members using The Cancer Genome Atlas data. Most CBX family members were found to be differentially expressed in various tumors, including HNSCC, compared to normal tissues. Multivariate Cox regression analysis showed that CBX3 expression is an independent prognostic factor for HNSCC patients. A nomogram based on CBX3 expression was constructed for use as a diagnostic indicator for HNSCC patients. We also used qPCR to validate the expression of CBX3. Results: Gene set enrichment analysis suggested that CBX3 participates in ataxia-telangiectasia mutated and Rad3-related protein kinase (ATR) activation and tumor progression. Analysis of immune infiltration indicated that CBX3 expression is negatively correlated with mast cells, DCs, immature DCs, and neutrophils. Conclusion: Our findings show that high CBX3 expression predicts poor prognosis in HNSCC and that CBX3 may act as an oncoprotein by activating ATR and affecting immune infiltration.

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Section: Discussionmentioning

confidence: 99%

CBX3 is a Prognostic Biomarker Correlated with ATR Activation and Immune Infiltration in Head and Neck Squamous Cell Carcinoma

Zhang¹,

Zhou²,

Liu³

2022

IJGM

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“…CBX3 is significantly upregulated in osteosarcoma tumor stem cells and facilitates their self-renewal [ 48 ]. Also, He Z. et al [ 49 ] have reported that esophageal squamous cell carcinoma (ESCC) acquire stem cell-like characteristics through CBX3-dependent inactivation of p53/p21 pathway.…”

Section: Discussionmentioning

confidence: 99%

Mining Transcriptomic Data to Uncover the Association between CBX Family Members and Cancer Stemness

Czerwińska

Maćkiewicz

2022

IJMS

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Genetic and epigenetic changes might facilitate the acquisition of stem cell-like phenotypes of tumors, resulting in worse patients outcome. Although the role of chromobox (CBX) domain proteins, a family of epigenetic factors that recognize specific histone marks, in the pathogenesis of several tumor types is well documented, little is known about their association with cancer stemness. Here, we have characterized the relationship between the CBX family members’ expression and cancer stemness in liver, lung, pancreatic, and uterine tumors using publicly available TCGA and GEO databases and harnessing several bioinformatic tools (i.e., Oncomine, GEPIA2, TISIDB, GSCA, UALCAN, R2 platform, Enrichr, GSEA). We demonstrated that significant upregulation of CBX3 and downregulation of CBX7 are consistently associated with enriched cancer stem-cell-like phenotype across distinct tumor types. High CBX3 expression is observed in higher-grade tumors that exhibit stem cell-like traits, and CBX3-associated gene expression profiles are robustly enriched with stemness markers and targets for c-Myc transcription factor regardless of the tumor type. Similar to high-stemness tumors, CBX3-overexpressing cancers manifest a higher mutation load. On the other hand, higher-grade tumors are characterized by the significant downregulation of CBX7, and CBX7-associated gene expression profiles are significantly depleted with stem cell markers. In contrast to high-stemness tumors, cancer with CBX7 upregulation exhibit a lower mutation burden. Our results clearly demonstrate yet unrecognized association of high CBX3 and low CBX7 expression with cancer stem cell-like phenotype of solid tumors.

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“…Aurora Kinase A, encoded by AURKA, is implicated in cell mitosis process, including centrosome maturation and spindle formation [ 44 , 45 ]. The anti-leukemic effect of Aurora kinase inhibitors was reported via inducing mitochondrial impairment [ 46 ], cell cycle arrest[ 47 ] etc. Preliminary clinical studies have been conducted to validate the efficacy and safety of Aurora kinase inhibitors in AML [ 48 – 50 ].…”

Section: Discussionmentioning

confidence: 99%

The landscape of gene co-expression modules correlating with prognostic genetic abnormalities in AML

Guo

Gao

et al. 2021

J Transl Med

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Background The heterogenous cytogenetic and molecular variations were harbored by AML patients, some of which are related with AML pathogenesis and clinical outcomes. We aimed to uncover the intrinsic expression profiles correlating with prognostic genetic abnormalities by WGCNA. Methods We downloaded the clinical and expression dataset from BeatAML, TCGA and GEO database. Using R (version 4.0.2) and ‘WGCNA’ package, the co-expression modules correlating with the ELN2017 prognostic markers were identified (R2 ≥ 0.4, p < 0.01). ORA detected the enriched pathways for the key co-expression modules. The patients in TCGA cohort were randomly assigned into the training set (50%) and testing set (50%). The LASSO penalized regression analysis was employed to build the prediction model, fitting OS to the expression level of hub genes by ‘glmnet’ package. Then the testing and 2 independent validation sets (GSE12417 and GSE37642) were used to validate the diagnostic utility and accuracy of the model. Results A total of 37 gene co-expression modules and 973 hub genes were identified for the BeatAML cohort. We found that 3 modules were significantly correlated with genetic markers (the ‘lightyellow’ module for NPM1 mutation, the ‘saddlebrown’ module for RUNX1 mutation, the ‘lightgreen’ module for TP53 mutation). ORA revealed that the ‘lightyellow’ module was mainly enriched in DNA-binding transcription factor activity and activation of HOX genes. The ‘saddlebrown’ module was enriched in immune response process. And the ‘lightgreen’ module was predominantly enriched in mitosis cell cycle process. The LASSO- regression analysis identified 6 genes (NFKB2, NEK9, HOXA7, APRC5L, FAM30A and LOC105371592) with non-zero coefficients. The risk score generated from the 6-gene model, was associated with ELN2017 risk stratification, relapsed disease, and prior MDS history. The 5-year AUC for the model was 0.822 and 0.824 in the training and testing sets, respectively. Moreover, the diagnostic utility of the model was robust when it was employed in 2 validation sets (5-year AUC 0.743–0.79). Conclusions We established the co-expression network signature correlated with the ELN2017 recommended prognostic genetic abnormalities in AML. The 6-gene prediction model for AML survival was developed and validated by multiple datasets.

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microRNA‐377 acts as a suppressor in esophageal squamous cell carcinoma through CBX3‐dependent P53/P21 pathway

Cited by 15 publications

References 39 publications

CBX3 is a Prognostic Biomarker Correlated with ATR Activation and Immune Infiltration in Head and Neck Squamous Cell Carcinoma

CBX3 is a Prognostic Biomarker Correlated with ATR Activation and Immune Infiltration in Head and Neck Squamous Cell Carcinoma

Mining Transcriptomic Data to Uncover the Association between CBX Family Members and Cancer Stemness

The landscape of gene co-expression modules correlating with prognostic genetic abnormalities in AML

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