Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chromobox homolog 7 (CBX7) plays an important role in gene transcription in a wide array of cellular processes, ranging from stem cell self-renewal and differentiation to tumor progression. CBX7 functions through its N-terminal chromodomain (ChD), which recognizes trimethylated lysine 27 of histone 3 (H3K27me3), a conserved epigenetic mark that signifies gene transcriptional repression. In this study, we report the discovery of small molecules that inhibit CBX7ChD binding to H3K27me3. Our crystal structures reveal the binding modes of these molecules that compete against H3K27me3 binding through interactions with key residues in the methyl-lysine binding pocket of CBX7ChD. We further show that a lead compound, MS37452, derepresses transcription of Polycomb repressive complex target gene p16/CDKN2A by displacing CBX7 binding to the INK4A/ARF locus in prostate cancer cells. These small molecules have the potential to be developed into high-potency chemical modulators that target CBX7 functions in gene transcription in different disease pathways.
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PMID:Small-molecule modulators of methyl-lysine binding for the CBX7 chromodomain. 2566 Feb 73

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