Details of Drug Off-Target (DOT)

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

• DOT Name: B-cell CLL/lymphoma 7 protein family member A (BCL7A)
• Gene Name: BCL7A
• Related Disease:
  B-cell lymphoma
  Breast cancer
  Breast carcinoma
  Burkitt lymphoma
  Chromosomal disorder
  Epithelial ovarian cancer
  Mycosis fungoides
  Neoplasm
  Non-hodgkin lymphoma
  Ovarian cancer
  Ovarian neoplasm
  Advanced cancer
  Epstein barr virus infection
  Primary cutaneous T-cell lymphoma
• UniProt ID: BCL7A_HUMAN
• Pfam ID: PF04714
• Sequence:
  MSGRSVRAETRSRAKDDIKRVMAAIEKVRKWEKKWVTVGDTSLRIYKWVPVTEPKVDDKN
  KNKKKGKDEKCGSEVTTPENSSSPGMMDMHDDNSNQSSIADASPIKQENSSNSSPAPEPN
  SAVPSDGTEAKVDEAQADGKEHPGAEDASDEQNSQSSMEHSMNSSEKVDRQPSGDSGLAA
  ETSAISQDLEGVPPSKKMKLEASQQNSEEM
• KEGG Pathway: ATP-dependent chromatin remodeling (hsa03082)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell lymphoma	DISIH1YQ	Strong	Genetic Variation	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Burkitt lymphoma	DIS9D5XU	Strong	Genetic Variation	[3]
Chromosomal disorder	DISM5BB5	Strong	Genetic Variation	[4]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[5]
Mycosis fungoides	DIS62RB8	Strong	Genetic Variation	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Genetic Variation	[1]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[5]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[8]
Epstein barr virus infection	DISOO0WT	Limited	Altered Expression	[7]
Primary cutaneous T-cell lymphoma	DIS35WVW	Limited	Posttranslational Modification	[9]

2 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 B-cell CLL/lymphoma 7 protein family member A (BCL7A).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of B-cell CLL/lymphoma 7 protein family member A (BCL7A).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of B-cell CLL/lymphoma 7 protein family member A (BCL7A).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of B-cell CLL/lymphoma 7 protein family member A (BCL7A).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of B-cell CLL/lymphoma 7 protein family member A (BCL7A).	[13]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of B-cell CLL/lymphoma 7 protein family member A (BCL7A).	[14]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of B-cell CLL/lymphoma 7 protein family member A (BCL7A).	[15]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of B-cell CLL/lymphoma 7 protein family member A (BCL7A).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of B-cell CLL/lymphoma 7 protein family member A (BCL7A).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of B-cell CLL/lymphoma 7 protein family member A (BCL7A).	[18]

References

• [1] Risk of non-Hodgkin lymphoma associated with germline variation in genes that regulate the cell cycle, apoptosis, and lymphocyte development.Cancer Epidemiol Biomarkers Prev. 2009 Apr;18(4):1259-70. doi: 10.1158/1055-9965.EPI-08-1037. Epub 2009 Mar 31.
• [2] Involvement of bcl-2 and p21waf1 proteins in response of human breast cancer cell clones to Tomudex.Br J Cancer. 1999 Sep;81(2):252-60. doi: 10.1038/sj.bjc.6690685.
• [3] The whole-genome landscape of Burkitt lymphoma subtypes.Blood. 2019 Nov 7;134(19):1598-1607. doi: 10.1182/blood.2019001880.
• [4] Molecular cloning of complex chromosomal translocation t(8;14;12)(q24.1;q32.3;q24.1) in a Burkitt lymphoma cell line defines a new gene (BCL7A) with homology to caldesmon.Blood. 1996 Apr 15;87(8):3124-34.
• [5] Low BCL7A expression predicts poor prognosis in ovarian cancer.J Ovarian Res. 2019 May 10;12(1):41. doi: 10.1186/s13048-019-0518-0.
• [6] Array-based comparative genomic hybridization in early-stage mycosis fungoides: recurrent deletion of tumor suppressor genes BCL7A, SMAC/DIABLO, and RHOF.Genes Chromosomes Cancer. 2008 Dec;47(12):1067-75. doi: 10.1002/gcc.20601.
• [7] Genipin as a novel chemical activator of EBV lytic cycle.J Microbiol. 2015 Feb;53(2):155-65. doi: 10.1007/s12275-015-4672-9. Epub 2015 Jan 28.
• [8] The Tumor Suppressor BCL7B Functions in the Wnt Signaling Pathway.PLoS Genet. 2015 Jan 8;11(1):e1004921. doi: 10.1371/journal.pgen.1004921. eCollection 2015 Jan.
• [9] Epigenetic profiling of cutaneous T-cell lymphoma: promoter hypermethylation of multiple tumor suppressor genes including BCL7a, PTPRG, and p73.J Clin Oncol. 2005 Jun 10;23(17):3886-96. doi: 10.1200/JCO.2005.11.353. Epub 2005 May 16.
• [10] 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.
• [11] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [12] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [13] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [14] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [15] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [16] 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.
• [17] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [18] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.