Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glioblastomas (GBM) are the most malignant form of astrocytomas which are difficult to treat and portend a grave clinical course and poor prognosis. In this study, we identified Chromobox homolog 7 (Cbx7), a member of Polycomb Repressive Complex 1 (PRC1), as a downregulated gene in GBM owing to its promoter hypermethylation. Bisulphite sequencing and methylation inhibitor treatment established the hypermethylation of Cbx7 in GBM. Exogenous overexpression of Cbx7 induced cell death, inhibited cell proliferation, colony formation and migration/invasion of the glioma cells. GSEA of Cbx7 regulated genes identified Cbx7 as a repressor of transcription co-activators YAP/TAZ, the inhibitory targets of the Hippo signalling pathway. In good correlation, the exogenous expression of Cbx7 repressed the YAP/TAZ-dependent transcription and downregulated CTGF, a bonafide YAP/TAZ target. We also observed reduced levels of phospho-JNK in Cbx7 expressing cells. Additionally, CTGF silencing and pharmacological inhibition of JNK also inhibited glioma cell migration. Further, Cbx7 failed to inhibit cell migration significantly in the presence of exogenously overexpressed CTGF or constitutively active JNK. Thus, our study identifies Cbx7 as an inhibitor of glioma cell migration through its inhibitory effect on YAP/TAZ-CTGF-JNK signalling axis and underscores the importance of epigenetic inactivation of Cbx7 in gliomagenesis.
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PMID:Cbx7 is epigenetically silenced in glioblastoma and inhibits cell migration by targeting YAP/TAZ-dependent transcription. 2729 Oct 91

Chromobox homolog 7 (CBX7) cooperates with other polycomb group (PcG) proteins to maintain target genes in a silenced state. However, the precise role of CBX7 in tumor progression is still controversial. We found that the expression of CBX7 in four public databases was significantly lower in high grade glioma (HGG). The reduced expression of CBX7 correlated with poor outcome in HGG patients. Both KEGG and GO analyses indicated that genes that were negatively correlated to CBX7 were strongly associated with the cell cycle pathway. We observed that decreased CBX7 protein levels enhanced glioma cells proliferation, migration and invasion. Then, we verified that CBX7 overexpression arrested cells in the G0/G1 phase. Moreover, we demonstrated that the underlying mechanism involved in CBX7 induced repression of CCNE1 promoter requiring the recruitment of histone deacetylase 2 (HADC2). Finally, in vivo bioluminescence imaging and survival times of nude mice revealed that CBX7 behaved as a tumor suppressor in gliomas. In summary, our results validate the assumption that CBX7 is a tumor suppressor of gliomas. Moreover, CBX7 is a potential and novel prognostic biomarker in glioma patients. We also clarified that CBX7 silences CCNE1 via the combination of CCNE1 promoter and the recruitment of HDAC2.
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PMID:CBX7 is a glioma prognostic marker and induces G1/S arrest via the silencing of CCNE1. 2846 Apr 53