Chromobox 4 facilitates tumorigenesis of lung adenocarcinoma through the Wnt/β-catenin pathway

Wang, Zuoyun; Fang, Zhaoyuan; Chen, Gaobin; Liu, Bo; Xu, Jinjin; Li, Fēi; Li, Fuming; Liu, Hongyan; Zhang, Haoen; Sun, Yihua; Tian, Gang; Chen, Haiquan; Xu, Guoliang; Zhang, Lei; Hu, Liang; Ji, Hongbin

doi:10.1016/j.neo.2020.12.005

Cited by 20 publications

(27 citation statements)

References 51 publications

(33 reference statements)

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“…CBX4 is the most studied member of the CBX family. CBX4 has been reported to up-regulate in multiple human tumors including lung adenocarcinoma ( 50 ), osteosarcoma ( 51 ), breast cancer ( 52 ), and cervical cancer ( 53 ). And the overexpression of CBX4 has been reported to predict shorter OS in several cancers ( 54 , 55 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Expression and Prognosis Value of Chromobox Family Members in Clear Cell Renal Cell Carcinoma

Zhu

et al. 2021

Front. Oncol.

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Clear cell renal cell carcinoma (ccRCC) accounts for 80% of all renal cancers and has a poor prognosis. Chromobox (CBX) family protein expression has been reported in a variety of human malignancies, but the roles of CBXs in ccRCC remain unclear. In this study, by using ONCOMINE, UALCAN, GEPIA, Kaplan-Meier Plotter, cBioPortal, and TIMER, we found the transcriptional levels of CBX3 and CBX4 in ccRCC tissues were significantly higher than those in normal kidney tissues, whereas the transcriptional levels of CBX1, CBX5, CBX6, and CBX7 were significantly reduced in ccRCC tissues. The promoters of CBX2, CBX3, CBX4, CBX5, CBX6, CBX7, and CBX8 were hypermethylated, whereas the CBX1 promoter was hypomethylated in ccRCC. The expression of CBX1, CBX3, CBX4, CBX5, CBX6, and CBX7 was significantly associated with clinicopathological parameters in ccRCC patients. ccRCC patients with high expression levels of CBX3, CBX4, and CBX8 and low expression levels of CBX1, CBX5, CBX6, and CBX7 showed a strong association with poor overall survival. Genetic alterations in CBXs were correlated with poor overall survival and disease-free survival in patients with ccRCC. Moreover, we found significant associations between the expression of CBXs and infiltration of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells). Our results provide novel insights into the development of CBX-based biomarkers and therapeutic targets for ccRCC.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Expression and Prognosis Value of Chromobox Family Members in Clear Cell Renal Cell Carcinoma

Zhu

et al. 2021

Front. Oncol.

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“…25 hPC2 gene expression is markedly upregulated in many types of human cancers, CBX4 promotes cell cycle progression, and mediates tumor growth and metastasis. [26][27][28][29] This evidence suggests that hPC2 plays an oncogenic role and serves as a potential therapeutic target. However, there have been conflicting results regarding tumor metastasis, CBX4 inhibits metastasis by directly repressing the transcription factor RUNX2 in colorectal cancer, in contrast, CBX4 promotes the invasion and metastasis of malignancies including osteosarcoma, breast cancer, and prostate carcinoma.…”

Section: Discussionmentioning

confidence: 97%

“…Therapeutic responses were evaluated based on the WHO criteria. Local tumor recurrence and regional lymph node invasion was observed in 29 4. Analyses of OS demonstrated that hPC2 expression was a prognostic factor for T3-T4 (p=0.005, Figure 4A), N2-N3 (p=0.004, Figure 4B) and clinical stages III-IV (p=0.007, Figure 4C).…”

Section: Relationship Between Hpc2 Expression and Clinical Outcomesmentioning

confidence: 99%

Human Polycomb Protein 2 (hPC2) as a Novel Independent Prognostic Marker in Nasopharyngeal Carcinoma

Wu¹,

Yang²,

Hou³

et al. 2021

CMAR

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Purpose: Human polycomb protein 2(hPC2) is a vital component of polycomb repressive complex 1(PRC1). It plays a critical role in tumorigenesis and progression. However, whether HPC2 expression affects the prognosis of patients with nasopharyngeal carcinoma (NPC) is currently unclear. In the present study, we investigated the expression of hPC2and elucidated its clinical prognostic significance in NPC. Patients and Methods: The expression of hPC2 in 180 NPCs samples was examined by immunohistochemistry (IHC) and evaluated by H-score staining intensity. Receiver operator characteristic (ROC) curve analysis was performed to determine cut-off values of hPC2 expression. The chi-square test, Kaplan-Meier (Log rank test), and the Cox proportional hazards model were utilized to analyze the data. Results: We found hPC2 is highly expressed in 48.3% of NPC specimens, which significantly correlated with T stage (p=0.032), N stage (p=0.006), and clinical stage (p=0.003). Kaplan-Meier analysis indicated that NPCs with high hPC2 expression tended to have a lower cumulative rates of overall survival (OS, p<0.001), recurrence-free survival (RFS, p=0.001), and distant metastasis-free survival (DMFS, p=0.003). In the NPCs subgroup, T3-T4, N2-N3, and stages III-IV, high hPC2 expression also had a prognostic impact on worse outcome in terms of OS, RFS, and DMFS. More importantly, multivariate analyses demonstrated that hPC2 expression was an independent prognostic factor for OS (hazard ratio [HR], 95% (confidence interval [CI]), p=0.001), RFS (HR, 95% CI, p=0.018), and DMFS (HR, 95% CI, p=0.022). Conclusion:We present evidence that high expression of hPC2 correlated with poorer prognosis in NPC. hPC2 could serve as a novel prognostic biomarker and might be a promising therapeutic target for NPC.

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“…Polycomb group (PcG) proteins have been revealed as the key transcriptional repressors that promote epigenetic silencing of targets, including polycomb-repressive complexes (PRC) PRC1 and PRC2 (24). Particularly, polycomb chromobox (CBX) proteins participate in the PRC1 complex and grant the distinct biological roles for PRC1 (25)(26)(27). Meanwhile, CBX proteins may function as oncogenic drivers or tumorsuppressive factors in a cancer-type-dependent manner.…”

Section: Introductionmentioning

confidence: 99%

Chromobox 4 (CBX4) promotes tumor progression and stemness via activating CDC20 in gastric cancer

Chen

Wang

et al. 2022

J Gastrointest Oncol

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Background: The Chromobox homolog 4 (CBX4) has been found to be overexpressed in multiple malignancies. However, the associations between CBX4 and gastric cancer (GC) have remained unclear. This study aimed to determine the biological roles of CBX4 in GC and identify effective therapeutic targets. Methods:The 3-(4,5-dimethylthiazol-2-yl) (MTT) assays were used to screen CBX family members.Differential analysis was utilized to evaluate the CBX4 levels. Kaplan-Meier analysis was used to perform prognostic analysis. Western blotting assay, quantitative polymerase chain reaction (qPCR) assay and immunohistochemistry (IHC) were used to assess CBX4 expressions. Colony formation assay, Cell Counting Kit-8 (CCK-8) assay, and Transwell assay were used to assess progression features of cells. The tail vein injection model was utilized to determine the metastatic efficacy of GC cells. Tumor sphere formation assay was used to assess tumor stemness maintenance ability. Chromatin immunoprecipitation (ChIP)-qPCR assay was used to evaluate the associations between CBX4 and CDC20. A subcutaneous tumor model was used to assess the in vivo growth ability of GC. Results:The MTT assay revealed that only CBX4 inhibition could lead to notable restriction of GC growth, as compared to others. Differential analysis suggested that CBX4 was upregulated in tumor samples relative to normal tissues. Less favorable overall survival (OS) outcomes were noticed in GC patients with high CBX4 in comparison to those with low CBX4. High CBX4 could notably enhance cell proliferation capacity, migration ability, and in vivo metastatic efficacy. Gene set enrichment analysis (GSEA) indicated the relationships between CBX4 and GC stemness, and CBX4 overexpression could remarkably elevate self-renewal ability of GC cells. In addition, CBX4 could mainly promote CDC20 messenger RNA (mRNA) levels, and targeting CBX4 suppressed the relative CDC20 levels. The ChIP-qPCR assay further demonstrated that CBX4 coordinated with H3K4me3 to bind at the CDC20 promoter region. Additionally, CBX4 depended on CDC20 to drive GC growth. Lastly, downregulated CBX4 could notably inhibit the growth of GC in vivo.Conclusions: This study highlights the oncogenic roles of CBX4 in GC. CBX4 activates CDC20 to maintain stemness features of GC, thereby creating therapeutic vulnerabilities in the treatment of GC.

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Chromobox 4 facilitates tumorigenesis of lung adenocarcinoma through the Wnt/β-catenin pathway

Cited by 20 publications

References 51 publications

Comprehensive Analysis of the Expression and Prognosis Value of Chromobox Family Members in Clear Cell Renal Cell Carcinoma

Comprehensive Analysis of the Expression and Prognosis Value of Chromobox Family Members in Clear Cell Renal Cell Carcinoma

Human Polycomb Protein 2 (hPC2) as a Novel Independent Prognostic Marker in Nasopharyngeal Carcinoma

Chromobox 4 (CBX4) promotes tumor progression and stemness via activating CDC20 in gastric cancer

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