CBX2 Regulates Proliferation and Apoptosis via the Phosphorylation of YAP in Hepatocellular Carcinoma

Mao, Jiakai; Tian, Yu; Wang, Cheng‐Ye; Jiang, Ke‐Jian; Li, Rui; Yao, Yifan; Zhang, Rixin; Sun, Da; Ling, Rui; Gao, Zhenming; Wang, Qi; Wang, Liming

doi:10.7150/jca.31845

Cited by 72 publications

(73 citation statements)

References 33 publications

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“…In 2014, Clermont et al (32) initially identified an oncogenic role for CBX2 through a meta-analysis of gene transcription in human cancers. Aberrantly high CBX2 levels are expressed in phenotypically diverse tumours such as breast cancer, hepatocellular cancer, oral cancer, ovarian cancer and lung cancer, for which it serves as a biomarker (21)(22)(23)(24)(25). Conversely, little is known about the expression or function of CBX2 in OSCC.…”

Section: Discussionmentioning

confidence: 99%

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Chromobox 2 Expression Predicts Prognosis After Curative Resection of Oesophageal Squamous Cell Carcinoma

Ueda

Kanda

Sato

et al. 2020

Cancer Genomics Proteomics

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Background/Aim: To investigate the function of chromobox 2 (CBX2) in oesophageal squamous cell carcinoma (OSCC). Materials and Methods: We used real-time quantitative reverse transcription PCR (qRT-PCR) and immunohistochemistry to determine CBX2 expression levels in 13 human OSCC cell lines and clinical specimens of two independent cohorts of patients with OSCC. Results: PCR array analysis revealed that CBX2 was co-ordinately expressed with WNT5B in OSCC cell lines. RT-qPCR analysis of clinical samples revealed a high tumour-specific CBX2 expression compared with normal oesophageal tissues. High CBX2 expression was significantly associated with shorter disease-specific survival, hematogenous recurrence, and overall recurrence. Analysis of tissue microarrays of one cohort revealed that patients with higher CBX2 levels tended to have a shorter disease-specific survival. Conclusion: CBX2 overexpression in OSCC tissues may serve as a novel biomarker for predicting survival and hematogenous recurrence. The main histopathological subtypes of oesophageal carcinoma, the sixth leading cause of cancer-related mortality worldwide (1), are adenocarcinoma and oesophageal squamous cell carcinoma (OSCC). The latter is the predominant subtype in Asia and Africa (2). OSCC is generally associated with poor prognosis, mainly because of its high potential to metastasize, which accounts for its dismal overall survival rate of <40%, despite radical treatment (3). A primary goal of efforts to improve the management of OSCC and patients' outcomes is to develop methods that accurately predict the risk of recurrence and survival after curative oesophageal resection (4, 5). Specific biomarkers that predict the recurrence pattern of OSCC, particularly for hematogenous recurrence after radical treatment, will likely contribute to improving patients' outcomes and are therefore the focus of our research. We the aim to identify novel biomarkers, we first focused on the chromobox 2 (CBX2) gene, a member of the chromobox (CBX) gene family, because of its reported association with certain cancers (6-8). CBX2 encodes a subunit of the polycomb group (PcG), whose members form complexes that mediate homeostasis (9). These proteins regulate the expression of numerous genes that control the maintenance, differentiation and proliferation of adult stem cells and cancer cells (10). Biochemical characterization led to the categorization of PcG complexes into two subtypes: Polycomb repressive complex (PRC) 1 and PRC2 (6, 11, 12). The CBX gene family comprises CBX2, CBX4, CBX6, CBX7 and CBX8, which encode components of PRC1 (11). PRC1 members are associated with tumourigenesis. For example, CBX4 plays important roles in cellular proliferation and in the repair of DNA damage in certain human tumours (13, 14). CBX6 was identified as a susceptibility loci by a genome-wide association study on bladder cancer (15). Numerous studies have shown that CBX7 is specifically 391 This article is freely accessible online.

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Section: Discussionmentioning

confidence: 99%

“…expressed in human tumours, including brain cancer (16), colon cancer (17), lung cancer (18) and gastric cancer (19); and CBX8 is involved in the pathogenesis of leukaemia (20). Although CBX2 has been studied in multiple cancers (21)(22)(23)(24)(25), its role in OSCC is unknown.…”

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confidence: 99%

Chromobox 2 Expression Predicts Prognosis After Curative Resection of Oesophageal Squamous Cell Carcinoma

Ueda

Kanda

Sato

et al. 2020

Cancer Genomics Proteomics

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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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“…CBX2 is highly expressed in human HCC tissues and is associated with poor prognosis in patients with HCC [6]. CBX2 is a crucial component of the polycomb group complex, polycomb repressive complex 1 (PRC1), which is involved in human carcinogenesis [6].…”

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confidence: 99%

Prognostic four-gene signature for overall survival in patients with hepatocellular carcinoma

Yokosuka

Moriyama

2019

Hepatol Int

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CBX2 Regulates Proliferation and Apoptosis via the Phosphorylation of YAP in Hepatocellular Carcinoma

Cited by 72 publications

References 33 publications

Chromobox 2 Expression Predicts Prognosis After Curative Resection of Oesophageal Squamous Cell Carcinoma

Chromobox 2 Expression Predicts Prognosis After Curative Resection of Oesophageal Squamous Cell Carcinoma

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

Prognostic four-gene signature for overall survival in patients with hepatocellular carcinoma

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