Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGJVU0C)

• DOT Name: Bladder cancer-associated protein (BLCAP)
• Synonyms: Bladder cancer 10 kDa protein; Bc10
• Gene Name: BLCAP
• Related Disease:
  Advanced cancer
  Astrocytoma
  Bladder cancer
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Carcinoma
  Cervical cancer
  Cervical carcinoma
  Hepatocellular carcinoma
  Medullary thyroid gland carcinoma
  Neoplasm
  Osteosarcoma
  Tarsal-carpal coalition syndrome
  Urinary bladder cancer
  Urinary bladder neoplasm
  Childhood kidney Wilms tumor
  Wilms tumor
• UniProt ID: BLCAP_HUMAN
• Pfam ID: PF06726
• Sequence:
  MYCLQWLLPVLLIPKPLNPALWFSHSMFMGFYLLSFLLERKPCTICALVFLAALFLICYS
  CWGNCFLYHCSDSPLPESAHDPGVVGT
• Function: May regulate cell proliferation and coordinate apoptosis and cell cycle progression via a novel mechanism independent of both p53/TP53 and NF-kappa-B.
• Tissue Specificity: Ubiquitous. Expressed in cervical tissues. Down-regulated in bladder invasive carcinoma, renal cell carcinoma and in primary cervical carcinoma.

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Astrocytoma	DISL3V18	Strong	Altered Expression	[2]
Bladder cancer	DISUHNM0	Strong	Genetic Variation	[3]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[4]
Carcinoma	DISH9F1N	Strong	Biomarker	[5]
Cervical cancer	DISFSHPF	Strong	Genetic Variation	[5]
Cervical carcinoma	DIST4S00	Strong	Genetic Variation	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[6]
Medullary thyroid gland carcinoma	DISHBL3K	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[1]
Tarsal-carpal coalition syndrome	DISY90L2	Strong	Altered Expression	[8]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[9]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[9]
Childhood kidney Wilms tumor	DIS0NMK3	Limited	Altered Expression	[10]
Wilms tumor	DISB6T16	Limited	Altered Expression	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Bladder cancer-associated protein (BLCAP).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Bladder cancer-associated protein (BLCAP).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Bladder cancer-associated protein (BLCAP).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Bladder cancer-associated protein (BLCAP).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Bladder cancer-associated protein (BLCAP).	[16]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Bladder cancer-associated protein (BLCAP).	[17]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Bladder cancer-associated protein (BLCAP).	[18]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Bladder cancer-associated protein (BLCAP).	[19]
Phenol	DM1QSM3	Phase 2/3	Phenol decreases the expression of Bladder cancer-associated protein (BLCAP).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Bladder cancer-associated protein (BLCAP).	[21]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Bladder cancer-associated protein (BLCAP).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Bladder cancer-associated protein (BLCAP).	[23]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Bladder cancer-associated protein (BLCAP).	[24]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Bladder cancer-associated protein (BLCAP).	[25]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Bladder cancer-associated protein (BLCAP).	[26]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Bladder cancer-associated protein (BLCAP).	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Bladder cancer-associated protein (BLCAP).	[15]

References

• [1] Immunoexpression analysis and prognostic value of BLCAP in breast cancer.PLoS One. 2012;7(9):e45967. doi: 10.1371/journal.pone.0045967. Epub 2012 Sep 25.
• [2] Human BLCAP transcript: new editing events in normal and cancerous tissues.Int J Cancer. 2010 Jul 1;127(1):127-37. doi: 10.1002/ijc.25022.
• [3] Aristolochic acid I interferes with the expression of BLCAP tumor suppressor gene in human cells.Toxicol Lett. 2018 Jul;291:129-137. doi: 10.1016/j.toxlet.2018.03.032. Epub 2018 Apr 12.
• [4] Long non-coding RNA MALAT1 regulates BLCAP mRNA expression through binding to miR-339-5p and promotes poor prognosis in breast cancer.Biosci Rep. 2019 Feb 15;39(2):BSR20181284. doi: 10.1042/BSR20181284. Print 2019 Feb 28.
• [5] A-to-I RNA editing of BLCAP lost the inhibition to STAT3 activation in cervical cancer.Oncotarget. 2017 Jun 13;8(24):39417-39429. doi: 10.18632/oncotarget.17034.
• [6] RNA over-editing of BLCAP contributes to hepatocarcinogenesis identified by whole-genome and transcriptome sequencing.Cancer Lett. 2015 Feb 28;357(2):510-9. doi: 10.1016/j.canlet.2014.12.006. Epub 2014 Dec 8.
• [7] Upregulated miR-9-3p Promotes Cell Growth and Inhibits Apoptosis in Medullary Thyroid Carcinoma by Targeting BLCAP.Oncol Res. 2017 Sep 21;25(8):1215-1222. doi: 10.3727/096504016X14791715355957. Epub 2016 Nov 17.
• [8] bc10: A novel human bladder cancer-associated protein with a conserved genomic structure downregulated in invasive cancer.Int J Cancer. 2002 Apr 1;98(4):539-46. doi: 10.1002/ijc.10244.
• [9] Identification of BLCAP as a novel STAT3 interaction partner in bladder cancer.PLoS One. 2017 Nov 30;12(11):e0188827. doi: 10.1371/journal.pone.0188827. eCollection 2017.
• [10] Selective methylation of CpGs at regulatory binding sites controls NNAT expression in Wilms tumors.PLoS One. 2013 Jun 25;8(6):e67605. doi: 10.1371/journal.pone.0067605. Print 2013.
• [11] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [12] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [13] 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.
• [14] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [15] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [16] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [17] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [18] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [19] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [20] Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
• [21] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [22] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [23] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [24] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [25] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.
• [26] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.
• [27] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.