Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6PMJIK)

• DOT Name: ETS translocation variant 1 (ETV1)
• Synonyms: Ets-related protein 81
• Gene Name: ETV1
• Related Disease:
  Colorectal carcinoma
  Colorectal neoplasm
  Adenocarcinoma
  Advanced cancer
  Arrhythmia
  Atrial fibrillation
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma of esophagus
  Clear cell renal carcinoma
  Desmoplastic small round cell tumor
  Esophageal adenocarcinoma
  Esophageal cancer
  Ewing sarcoma
  Hantavirus infection
  Lung neoplasm
  Myelodysplastic syndrome
  Neoplasm of esophagus
  Prostate neoplasm
  Renal cell carcinoma
  Skin cancer
  Soft tissue neoplasm
  Metastatic malignant neoplasm
  Neuroblastoma
  Triple negative breast cancer
  Melanoma
  Squamous cell carcinoma
• UniProt ID: ETV1_HUMAN
• PDB ID: 4AVP; 4BNC; 5ILS
• Pfam ID: PF00178 ; PF04621
• Sequence:
  MDGFYDQQVPYMVTNSQRGRNCNEKPTNVRKRKFINRDLAHDSEELFQDLSQLQETWLAE
  AQVPDNDEQFVPDYQAESLAFHGLPLKIKKEPHSPCSEISSACSQEQPFKFSYGEKCLYN
  VSAYDQKPQVGMRPSNPPTPSSTPVSPLHHASPNSTHTPKPDRAFPAHLPPSQSIPDSSY
  PMDHRFRRQLSEPCNSFPPLPTMPREGRPMYQRQMSEPNIPFPPQGFKQEYHDPVYEHNT
  MVGSAASQSFPPPLMIKQEPRDFAYDSEVPSCHSIYMRQEGFLAHPSRTEGCMFEKGPRQ
  FYDDTCVVPEKFDGDIKQEPGMYREGPTYQRRGSLQLWQFLVALLDDPSNSHFIAWTGRG
  MEFKLIEPEEVARRWGIQKNRPAMNYDKLSRSLRYYYEKGIMQKVAGERYVYKFVCDPEA
  LFSMAFPDNQRPLLKTDMERHINEEDTVPLSHFDESMAYMPEGGCCNPHPYNEGYVY
• Function: Transcriptional activator that binds to DNA sequences containing the consensus pentanucleotide 5'-CGGA[AT]-3'. Required for olfactory dopaminergic neuron differentiation; may directly activate expression of tyrosine hydroxylase (TH).
• Tissue Specificity: Very highly expressed in brain, highly expressed in testis, lung and heart, moderately in spleen, small intestine, pancreas and colon, weakly in liver, prostate and thymus, very weakly in skeletal muscle, kidney and ovary and not in placenta and peripheral blood leukocytes.
• KEGG Pathway: Transcriptio.l misregulation in cancer (hsa05202)

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[1]
Colorectal neoplasm	DISR1UCN	Definitive	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Arrhythmia	DISFF2NI	Strong	Altered Expression	[4]
Atrial fibrillation	DIS15W6U	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[6]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[7]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[8]
Desmoplastic small round cell tumor	DISLI2ME	Strong	Genetic Variation	[9]
Esophageal adenocarcinoma	DISODWFP	Strong	Altered Expression	[7]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[7]
Ewing sarcoma	DISQYLV3	Strong	Altered Expression	[3]
Hantavirus infection	DISZFTMH	Strong	Altered Expression	[10]
Lung neoplasm	DISVARNB	Strong	Biomarker	[11]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[12]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[7]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[13]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[8]
Skin cancer	DISTM18U	Strong	Biomarker	[14]
Soft tissue neoplasm	DISP2OHE	Strong	Genetic Variation	[9]
Metastatic malignant neoplasm	DIS86UK6	moderate	Altered Expression	[15]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[16]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[15]
Melanoma	DIS1RRCY	Limited	Altered Expression	[17]
Squamous cell carcinoma	DISQVIFL	Limited	Altered Expression	[18]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	ETS translocation variant 1 (ETV1) affects the response to substance of Temozolomide.	[38]
DTI-015	DMXZRW0	Approved	ETS translocation variant 1 (ETV1) affects the response to substance of DTI-015.	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of ETS translocation variant 1 (ETV1).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of ETS translocation variant 1 (ETV1).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of ETS translocation variant 1 (ETV1).	[20]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ETS translocation variant 1 (ETV1).	[21]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of ETS translocation variant 1 (ETV1).	[22]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of ETS translocation variant 1 (ETV1).	[23]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of ETS translocation variant 1 (ETV1).	[24]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of ETS translocation variant 1 (ETV1).	[25]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of ETS translocation variant 1 (ETV1).	[26]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of ETS translocation variant 1 (ETV1).	[27]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of ETS translocation variant 1 (ETV1).	[28]
PD-0325901	DM27D4J	Phase 2	PD-0325901 decreases the expression of ETS translocation variant 1 (ETV1).	[29]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of ETS translocation variant 1 (ETV1).	[31]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of ETS translocation variant 1 (ETV1).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ETS translocation variant 1 (ETV1).	[33]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of ETS translocation variant 1 (ETV1).	[34]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of ETS translocation variant 1 (ETV1).	[35]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of ETS translocation variant 1 (ETV1).	[36]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of ETS translocation variant 1 (ETV1).	[37]

References

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• [3] A novel PTPRZ1-ETV1 fusion in gliomas.Brain Pathol. 2020 Mar;30(2):226-234. doi: 10.1111/bpa.12776. Epub 2019 Aug 27.
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• [5] ER81-shRNA inhibits growth of triple-negative human breast cancer cell line MDA-MB-231 in vivo and in vitro.Asian Pac J Cancer Prev. 2012;13(5):2385-92. doi: 10.7314/apjcp.2012.13.5.2385.
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• [7] MK2 and ETV1 Are Prognostic Factors in Esophageal Adenocarcinomas.J Cancer. 2018 Jan 1;9(3):460-468. doi: 10.7150/jca.22310. eCollection 2018.
• [8] COP1 is downregulated in renal cell carcinoma (RCC) and inhibits the migration of RCC ACHN cells invitro.Mol Med Rep. 2016 Aug;14(2):1371-8. doi: 10.3892/mmr.2016.5373. Epub 2016 Jun 7.
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• [11] Crosstalk in competing endogenous RNA network reveals the complex molecular mechanism underlying lung cancer.Oncotarget. 2017 Aug 24;8(53):91270-91280. doi: 10.18632/oncotarget.20441. eCollection 2017 Oct 31.
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• [14] Epigenetic and genetic dissections of UV-induced global gene dysregulation in skin cells through multi-omics analyses.Sci Rep. 2017 Feb 17;7:42646. doi: 10.1038/srep42646.
• [15] miR-17-5p suppresses cell proliferation and invasion by targeting ETV1 in triple-negative breast cancer.BMC Cancer. 2017 Nov 10;17(1):745. doi: 10.1186/s12885-017-3674-x.
• [16] Ets transcription factors ER81 and Elk1 regulate the transcription of the human presenilin 1 gene promoter.Brain Res Mol Brain Res. 2003 May 12;113(1-2):57-66. doi: 10.1016/s0169-328x(03)00090-1.
• [17] miR-17 regulates melanoma cell motility by inhibiting the translation of ETV1.Oncotarget. 2015 Aug 7;6(22):19006-16. doi: 10.18632/oncotarget.4147.
• [18] Dualism of FGF and TGF- Signaling in Heterogeneous Cancer-Associated Fibroblast Activation with ETV1 as a Critical Determinant.Cell Rep. 2019 Aug 27;28(9):2358-2372.e6. doi: 10.1016/j.celrep.2019.07.092.
• [19] 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.
• [20] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [21] 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.
• [22] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [23] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [24] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [25] 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.
• [26] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [27] Iminoenamine based novel androgen receptor antagonist exhibited anti-prostate cancer activity in androgen independent prostate cancer cells through inhibition of AKT pathway. Chem Biol Interact. 2017 Sep 25;275:22-34. doi: 10.1016/j.cbi.2017.07.023. Epub 2017 Jul 27.
• [28] 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.
• [29] PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature. 2014 Oct 9;514(7521):247-51.
• [30] 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.
• [31] The BET bromodomain inhibitor JQ1 suppresses growth of pancreatic ductal adenocarcinoma in patient-derived xenograft models. Oncogene. 2016 Feb 18;35(7):833-45.
• [32] 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.
• [33] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
• [34] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [35] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [36] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.
• [37] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
• [38] Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.