Beyond EZH2: is the polycomb protein CBX2 an emerging target for anti-cancer therapy?

Jangal, Maïka; Lebeau, Benjamin; Witcher, Michael

doi:10.1080/14728222.2019.1627329

Cited by 28 publications

(30 citation statements)

References 113 publications

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“…These results were consistent with the CCLE database. As mentioned above, CBX2 has been proven by numerous researchers to affect cell proliferation by binding to the Ink4a/Arf locus [47]. Consistent with previous observations, the present in vitro experiments indicated that CBX2-knockdown signi cantly inhibited cell proliferation and invasion in HCT116 and HT29 cell lines.…”

Section: Discussionsupporting

confidence: 91%

Expression and prognostic significance of CBX2 in colorectal cancer: Database mining for CBX family members in malignancies

Zhou¹,

Xiong²,

Liu³

et al. 2021

Preprint

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Background: The Chromobox (CBX) domain protein family, a core component of polycomb repressive complexes 1, is involved in transcriptional repression, cell differentiation, and program development by binding to methylated histone tails. Each CBX family member plays a distinct role in various biological processes through their own specific chromatin domains, due to differences in conserved sequences of the CBX proteins. It has been demonstrated that colorectal cancer (CRC) is a multiple-step biological evolutionary process, whereas the roles of the CBX family in CRC remain largely unclear.Methods: In the present study, the expression and prognostic significance of the CBX family in CRC were systematically analyzed through a series of online databases, including Cancer Cell Line Encyclopedia (CCLE), Oncomine, Human Protein Atlas (HPA), and Gene Expression Profiling Interactive Analysis (GEPIA).Results: Most CBX proteins were found to be highly expressed in CRC, but only the elevated expression of CBX2 could be associated with poor prognosis in patients with CRC. Further examination of the role of CBX2 in CRC was performed through several in vitro experiments. CBX2 was overexpressed in CRC cell lines via the CCLE database and the results were verified by RT-qPCR. Moreover, the knockdown of CBX2 significantly suppressed CRC cell proliferation and invasion. Furthermore, the downregulation of CBX2 was found to promote CRC cell apoptosis. Conclusion: Based on these findings, CBX2 may function as an oncogene and potential prognostic biomarker. Thus, the association between the abnormal expression of CBX2 and the initiation of CRC deserves further exploration.

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Section: Discussionsupporting

confidence: 91%

Expression and prognostic significance of CBX2 in colorectal cancer: Database mining for CBX family members in malignancies

Zhou¹,

Xiong²,

Liu³

et al. 2021

Preprint

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“…Studies suggest that we can improve the clinical radiotherapy effect on LUAD by inhibiting the transcriptional regulation of HOXA10, thus prolonging survival. The other mRNA in the signature is CBX2, which is overexpressed in cancers, including breast cancer and hepatocellular carcinoma, and is significantly related to poor prognosis [24][25], indicating that its activity provides an advantages for the growth and development of cancer [26]. In addition, targeted therapy studies in non-small cell lung cancer clearly show that SMARCE1 inhibits EGFR expression, in part by modulating the level of the polycomb repressive complex component CBX2.…”

Section: Discussionmentioning

confidence: 99%

A signature related to lung adenocarcinoma prognosis: A study based on TCGA database

Wang¹,

Zhang²,

Zhang³

et al. 2020

Preprint

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Background: The intrinsic molecular subtypes of lung adenocarcinoma (LUAD) impact clinical treatment decision-making, but the molecular mechanisms are still unclear. Therefore, we aimed to identify sensitive biomarkers to evaluate LUAD patient prognosis. Methods: Differentially expressed RNAs from LUAD patients were obtained from The Cancer Genome Atlas (TCGA) database and they were used to construct a competitive endogenous RNA (ceRNA) network. Based on the examination of clinical data, long noncoding RNAs (lncRNAs) and mRNAs in the network were selected by univariate and multivariate Cox regression analysis. Finally, functional enrichment analysis was used to reveal prognostic signatures based on the classification into high and low-risk groups, survival analysis, and an independence test. Results: The ceRNA network consisted of 21 mRNAs, 53 lncRNAs, and 8 miRNAs that were selected from the differentially expressed RNAs identified. Next, based on univariate and multivariate Cox regression analysis, a prognostic signature, including two mRNAs (HOXA10 and CBX2) and four lncRNAs (LINC00460, LINC00330, DGCR5, and C14orf132) was constructed. Eventually, survival analysis showed that significant differences in survival rates between high and low-risk groups and the area under the curve (AUC) for three‐year survival was 0.714. Compared with clinical risk factors, including age, pathological stage, and TNM stage, our risk score had a higher prognostic value. Conclusion: By screening from a ceRNA network, we constructed a signature, including two mRNAs (HOXA10 and CBX2) and four lncRNAs (LINC00460, LINC00330, DGCR5, and C14orf132), that can be utilized as a prognostic biomarker in LUAD. This signature may provide options for clinical treatment.

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“…According to previous studies, CBXs are known to be involved in the occurrence and development of a diverse range of tumors through various pathways (9,10). For example, Han et al reported that CBX2 could act as a tumor promoter in osteosarcoma by targeting miRNA let-7a (11).…”

Section: Introductionmentioning

confidence: 99%

Prognosis and Immune Infiltration of Chromobox Family Genes in Sarcoma

et al. 2021

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BackgroundChromobox family genes (CBXs) are known to play roles in numerous modifications of the chromatin in order to inhibit the transcription of target genes. CBXs have been shown to be expressed at high levels in many types of cancer and can also serve as a target gene for therapeutic purposes. However, little is known about the expression and prognostic value of CBXs in human sarcomas.MethodsThe transcription level of CBXs was analyzed using the Oncomine dataset, and the differential expression of CBXs in sarcoma was reported by the Gene Expression Profiling Interactive Analysis (GEPIA) dataset. We also used the CCLE dataset to evaluate the expression of CBXs in a sarcoma cell line. The prognostic value of CBXs was analyzed using GEPIA and Kaplan–Meier analysis. In addition, the corrections between CBXs and their co-expressed genes were reported using Oncomine and GEPIA datasets. DAVID was used to perform GO function enrichment analysis for the CBXs and their co-expression genes. Finally, TIMER was used to analyze the immune cell infiltration of CBXs in patients with sarcoma.ResultsHP1-α/β/γ (CBX1/3/5) and CBX4/6/8 were found to be overexpressed in human sarcoma, and CBXs were upregulated in almost all the sarcoma cell line. The expression levels of HP1-α/β/γ (CBX1/3/5) and CBX7 were associated with overall survival (OS) in patients with sarcoma, while high expression levels of CBX7 were related to disease-free survival (DFS). In addition, the expression levels of CBX2/6/7 were related to recurrence-free survival (RFS). We also found that the CBX family was positively correlated with the infiltration of immune cells, including CD8+ T cells, CD4+ T cells, B cells, macrophages, neutrophils, and dendritic cells, in sarcoma.ConclusionsThe results from the present study indicated that CBXs were significantly associated with prognosis and immunological status in sarcoma. These data suggest that CBXs could serve as potential biomarkers for prognosis and immune infiltration in human sarcoma.

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Beyond EZH2: is the polycomb protein CBX2 an emerging target for anti-cancer therapy?

Cited by 28 publications

References 113 publications

Expression and prognostic significance of CBX2 in colorectal cancer: Database mining for CBX family members in malignancies

Expression and prognostic significance of CBX2 in colorectal cancer: Database mining for CBX family members in malignancies

A signature related to lung adenocarcinoma prognosis: A study based on TCGA database

Prognosis and Immune Infiltration of Chromobox Family Genes in Sarcoma

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