Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4U5V1T)

• DOT Name: Chromobox protein homolog 8 (CBX8)
• Synonyms: Polycomb 3 homolog; Pc3; hPc3; Rectachrome 1
• Gene Name: CBX8
• Related Disease:
  Breast cancer
  Breast carcinoma
  Carcinoma
  Carcinoma of esophagus
  Cervical cancer
  Cervical carcinoma
  Colon cancer
  Colon carcinoma
  Esophageal squamous cell carcinoma
  Hepatocellular carcinoma
  leukaemia
  Neoplasm
  Neuroblastoma
  Transitional cell carcinoma
  Urinary bladder cancer
  Urothelial carcinoma
  Colorectal carcinoma
  Metastatic malignant neoplasm
  Advanced cancer
  Schizophrenia
• UniProt ID: CBX8_HUMAN
• PDB ID: 2N4Q; 3I91; 5EQ0
• Pfam ID: PF17218 ; PF00385
• Sequence:
  MELSAVGERVFAAEALLKRRIRKGRMEYLVKWKGWSQKYSTWEPEENILDARLLAAFEER
  EREMELYGPKKRGPKPKTFLLKAQAKAKAKTYEFRSDSARGIRIPYPGRSPQDLASTSRA
  REGLRNMGLSPPASSTSTSSTCRAEAPRDRDRDRDRDRERDRERERERERERERERERER
  GTSRVDDKPSSPGDSSKKRGPKPRKELPDPSQRPLGEPSAGLGEYLKGRKLDDTPSGAGK
  FPAGHSVIQLARRQDSDLVQCGVTSPSSAEATGKLAVDTFPARVIKHRAAFLEAKGQGAL
  DPNGTRVRHGSGPPSSGGGLYRDMGAQGGRPSLIARIPVARILGDPEEESWSPSLTNLEK
  VVVTDVTSNFLTVTIKESNTDQGFFKEKR
• Function: Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility.
• KEGG Pathway: Polycomb repressive complex (hsa03083)
• Reactome Pathway:
  SUMOylation of DNA damage response and repair proteins (R-HSA-3108214)
  SUMOylation of transcription cofactors (R-HSA-3899300)
  SUMOylation of chromatin organization proteins (R-HSA-4551638)
  SUMOylation of RNA binding proteins (R-HSA-4570464)
  SUMOylation of DNA methylation proteins (R-HSA-4655427)
  RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known (R-HSA-8939243)
  Regulation of PTEN gene transcription (R-HSA-8943724)
  Oxidative Stress Induced Senescence (R-HSA-2559580)

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Carcinoma	DISH9F1N	Strong	Biomarker	[2]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[3]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[4]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[4]
Colon cancer	DISVC52G	Strong	Altered Expression	[5]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[5]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
leukaemia	DISS7D1V	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[9]
Transitional cell carcinoma	DISWVVDR	Strong	Biomarker	[10]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[11]
Urothelial carcinoma	DISRTNTN	Strong	Biomarker	[10]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[12]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[13]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[5]
Schizophrenia	DISSRV2N	No Known	Unknown	[14]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Chromobox protein homolog 8 (CBX8).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Chromobox protein homolog 8 (CBX8).	[19]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Chromobox protein homolog 8 (CBX8).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Chromobox protein homolog 8 (CBX8).	[21]

3 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Chromobox protein homolog 8 (CBX8).	[16]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Chromobox protein homolog 8 (CBX8).	[17]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Chromobox protein homolog 8 (CBX8).	[18]

References

• [1] Increased Expression of Circular RNA circ_0005230 Indicates Dismal Prognosis in Breast Cancer and Regulates Cell Proliferation and Invasion via miR-618/ CBX8 Signal Pathway.Cell Physiol Biochem. 2018;51(4):1710-1722. doi: 10.1159/000495675. Epub 2018 Nov 30.
• [2] CBX8 exhibits oncogenic properties and serves as a prognostic factor in hepatocellular carcinoma.Cell Death Dis. 2019 Jan 18;10(2):52. doi: 10.1038/s41419-018-1288-0.
• [3] CBX8, a novel DNA repair protein, promotes tumorigenesis in human esophageal carcinoma.Int J Clin Exp Pathol. 2014 Jul 15;7(8):4817-26. eCollection 2014.
• [4] CircRNA8924 Promotes Cervical Cancer Cell Proliferation, Migration and Invasion by Competitively Binding to MiR-518d-5p /519-5p Family and Modulating the Expression of CBX8.Cell Physiol Biochem. 2018;48(1):173-184. doi: 10.1159/000491716. Epub 2018 Jul 13.
• [5] m(6)A modification-mediated CBX8 induction regulates stemness and chemosensitivity of colon cancer via upregulation of LGR5.Mol Cancer. 2019 Dec 18;18(1):185. doi: 10.1186/s12943-019-1116-x.
• [6] CBX8 promotes tumorigenesis and confers radioresistance in esophageal squamous cell carcinoma cells through targeting APAF1.Gene. 2019 Aug 30;711:143949. doi: 10.1016/j.gene.2019.143949. Epub 2019 Jun 28.
• [7] The ENL moiety of the childhood leukemia-associated MLL-ENL oncoprotein recruits human Polycomb 3.Oncogene. 2001 Jan 25;20(4):411-9. doi: 10.1038/sj.onc.1204108.
• [8] Monomeric and Dimeric (68)Ga-Labeled Bombesin Analogues for Positron Emission Tomography (PET) Imaging of Tumors Expressing Gastrin-Releasing Peptide Receptors (GRPrs).J Med Chem. 2018 Mar 8;61(5):2062-2074. doi: 10.1021/acs.jmedchem.7b01856. Epub 2018 Feb 22.
• [9] The neurogene BTG2TIS21/PC3 is transactivated by DeltaNp73alpha via p53 specifically in neuroblastoma cells.J Cell Sci. 2005 Mar 15;118(Pt 6):1245-53. doi: 10.1242/jcs.01704. Epub 2005 Mar 1.
• [10] Chromobox homolog 8 is a predictor of muscle invasive bladder cancer and promotes cell proliferation by repressing the p53 pathway.Cancer Sci. 2017 Nov;108(11):2166-2175. doi: 10.1111/cas.13383. Epub 2017 Sep 25.
• [11] Inhibition of bladder cancer invasion by Sp1-mediated BTG2 expression via inhibition of DNA methyltransferase 1.FEBS J. 2014 Dec;281(24):5581-601. doi: 10.1111/febs.13099. Epub 2014 Oct 30.
• [12] CBX8 and CD96 Are Important Prognostic Biomarkers of Colorectal Cancer.Med Sci Monit. 2018 Nov 1;24:7820-7827. doi: 10.12659/MSM.908656.
• [13] CBX8 Suppresses Tumor Metastasis via Repressing Snail in Esophageal Squamous Cell Carcinoma.Theranostics. 2017 Aug 15;7(14):3478-3488. doi: 10.7150/thno.20717. eCollection 2017.
• [14] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [15] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [16] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [17] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [18] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [19] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [20] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [21] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.