Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY6TPWD)

• DOT Name: ETS homologous factor (EHF)
• Synonyms: hEHF; ETS domain-containing transcription factor; Epithelium-specific Ets transcription factor 3; ESE-3
• Gene Name: EHF
• Related Disease:
  Matthew-Wood syndrome
  Pancreatic cancer
  Pancreatic ductal carcinoma
  Abdominal aortic aneurysm
  Acute myocardial infarction
  Advanced cancer
  Deafness
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Malignant mesothelioma
  Ovarian cancer
  Ovarian neoplasm
  Prostate carcinoma
  Psoriasis
  Systemic lupus erythematosus
  Carcinoma
  Cystic fibrosis
  Gastric cancer
  Prostate neoplasm
  Pulmonary disease
  Sensorineural hearing loss disorder
  Stomach cancer
  Neoplasm
  Asthma
  Breast cancer
  Prostate cancer
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid gland papillary carcinoma
  Thyroid tumor
• UniProt ID: EHF_HUMAN
• Pfam ID: PF00178 ; PF02198
• Sequence:
  MILEGGGVMNLNPGNNLLHQPPAWTDSYSTCNVSSGFFGGQWHEIHPQYWTKYQVWEWLQ
  HLLDTNQLDANCIPFQEFDINGEHLCSMSLQEFTRAAGTAGQLLYSNLQHLKWNGQCSSD
  LFQSTHNVIVKTEQTEPSIMNTWKDENYLYDTNYGSTVDLLDSKTFCRAQISMTTTSHLP
  VAESPDMKKEQDPPAKCHTKKHNPRGTHLWEFIRDILLNPDKNPGLIKWEDRSEGVFRFL
  KSEAVAQLWGKKKNNSSMTYEKLSRAMRYYYKREILERVDGRRLVYKFGKNARGWRENEN
• Function: Transcriptional activator that may play a role in regulating epithelial cell differentiation and proliferation. May act as a repressor for a specific subset of ETS/AP-1-responsive genes and as a modulator of the nuclear response to mitogen-activated protein kinase signaling cascades. Binds to DNA sequences containing the consensus nucleotide core sequence GGAA. Involved in regulation of TNFRSF10B/DR5 expression through Ets-binding sequences on the TNFRSF10B/DR5 promoter. May contribute to development and carcinogenesis by acting as a tumor suppressor gene or anti-oncogene.
• Tissue Specificity: Expressed exclusively in tissues with a high content of epithelial cells. Highly expressed in salivary gland, mammary gland, prostate, and lung. Weakly expressed in kidney and colon. Not detected in heart, brain, placenta, liver, skeletal muscle, spleen, thymus, testis, ovary, small intestine or peripheral blood leukocytes.

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Matthew-Wood syndrome	DISA7HR7	Definitive	Biomarker	[1]
Pancreatic cancer	DISJC981	Definitive	Biomarker	[2]
Pancreatic ductal carcinoma	DIS26F9Q	Definitive	Biomarker	[1]
Abdominal aortic aneurysm	DISD06OF	Strong	Therapeutic	[3]
Acute myocardial infarction	DISE3HTG	Strong	Altered Expression	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Deafness	DISKCLH4	Strong	Biomarker	[5]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[6]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[7]
Malignant mesothelioma	DISTHJGH	Strong	Altered Expression	[8]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[6]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[6]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[7]
Psoriasis	DIS59VMN	Strong	Biomarker	[9]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[10]
Carcinoma	DISH9F1N	moderate	Genetic Variation	[8]
Cystic fibrosis	DIS2OK1Q	moderate	Biomarker	[11]
Gastric cancer	DISXGOUK	moderate	Biomarker	[12]
Prostate neoplasm	DISHDKGQ	moderate	Altered Expression	[13]
Pulmonary disease	DIS6060I	moderate	Biomarker	[11]
Sensorineural hearing loss disorder	DISJV45Z	moderate	Genetic Variation	[14]
Stomach cancer	DISKIJSX	moderate	Biomarker	[12]
Neoplasm	DISZKGEW	Disputed	Biomarker	[1]
Asthma	DISW9QNS	Limited	Genetic Variation	[15]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[7]
Prostate cancer	DISF190Y	Limited	Altered Expression	[7]
Thyroid cancer	DIS3VLDH	Limited	Altered Expression	[7]
Thyroid gland carcinoma	DISMNGZ0	Limited	Altered Expression	[7]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Altered Expression	[7]
Thyroid tumor	DISLVKMD	Limited	Altered Expression	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of ETS homologous factor (EHF).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of ETS homologous factor (EHF).	[17]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of ETS homologous factor (EHF).	[18]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of ETS homologous factor (EHF).	[19]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of ETS homologous factor (EHF).	[20]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of ETS homologous factor (EHF).	[21]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of ETS homologous factor (EHF).	[22]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of ETS homologous factor (EHF).	[23]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of ETS homologous factor (EHF).	[24]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of ETS homologous factor (EHF).	[26]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of ETS homologous factor (EHF).	[19]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of ETS homologous factor (EHF).	[27]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of ETS homologous factor (EHF).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of ETS homologous factor (EHF).	[25]

References

• [1] Tumoral EHF predicts the efficacy of anti-PD1 therapy in pancreatic ductal adenocarcinoma.J Exp Med. 2019 Mar 4;216(3):656-673. doi: 10.1084/jem.20180749. Epub 2019 Feb 7.
• [2] ESE3 Inhibits Pancreatic Cancer Metastasis by Upregulating E-Cadherin.Cancer Res. 2017 Feb 15;77(4):874-885. doi: 10.1158/0008-5472.CAN-16-2170. Epub 2016 Dec 6.
• [3] Inhibition of experimental abdominal aortic aneurysm in the rat by use of decoy oligodeoxynucleotides suppressing activity of nuclear factor kappaB and ets transcription factors.Circulation. 2004 Jan 6;109(1):132-8. doi: 10.1161/01.CIR.0000105725.61763.A2. Epub 2003 Dec 8.
• [4] Identification of Transcription Factor-Gene Regulatory Network in Acute Myocardial Infarction.Heart Lung Circ. 2017 Apr;26(4):343-353. doi: 10.1016/j.hlc.2016.06.1209. Epub 2016 Jul 26.
• [5] Extended high-frequency hearing enhances speech perception in noise.Proc Natl Acad Sci U S A. 2019 Nov 19;116(47):23753-23759. doi: 10.1073/pnas.1903315116. Epub 2019 Nov 4.
• [6] Knockdown of EHF inhibited the proliferation, invasion and tumorigenesis of ovarian cancer cells.Mol Carcinog. 2016 Jun;55(6):1048-59. doi: 10.1002/mc.22349. Epub 2015 Aug 10.
• [7] Increased expression of EHF contributes to thyroid tumorigenesis through transcriptionally regulating HER2 and HER3.Oncotarget. 2016 Sep 6;7(36):57978-57990. doi: 10.18632/oncotarget.11154.
• [8] Expression of the Ets transcription factor EHF in serous ovarian carcinoma effusions is a marker of poor survival.Hum Pathol. 2012 Apr;43(4):496-505. doi: 10.1016/j.humpath.2011.05.023. Epub 2011 Aug 19.
• [9] Integrated analysis of gene expression profiles identifies transcription factors potentially involved in psoriasis pathogenesis.J Cell Biochem. 2019 Aug;120(8):12582-12594. doi: 10.1002/jcb.28525. Epub 2019 Mar 1.
• [10] GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.Genes Immun. 2014 Sep;15(6):347-54. doi: 10.1038/gene.2014.23. Epub 2014 May 29.
• [11] Coordinate regulation of ELF5 and EHF at the chr11p13 CF modifier region.J Cell Mol Med. 2019 Nov;23(11):7726-7740. doi: 10.1111/jcmm.14646. Epub 2019 Sep 26.
• [12] miR?06 inhibits cancer initiating cells by targeting EHF in gastric cancer.Oncol Rep. 2017 Sep;38(3):1688-1694. doi: 10.3892/or.2017.5794. Epub 2017 Jul 6.
• [13] The ETS factor ESE3/EHF represses IL-6 preventing STAT3 activation and expansion of the prostate cancer stem-like compartment.Oncotarget. 2016 Nov 22;7(47):76756-76768. doi: 10.18632/oncotarget.12525.
• [14] Auditory Outcomes in Patients Who Received Proton Radiotherapy for Craniopharyngioma.Am J Audiol. 2018 Sep 12;27(3):306-315. doi: 10.1044/2018_AJA-18-0026.
• [15] Polymorphisms of EHF-ELF5 genomic region and its association with pediatric asthma in the Taiwanese population.J Microbiol Immunol Infect. 2016 Dec;49(6):879-884. doi: 10.1016/j.jmii.2014.11.016. Epub 2014 Dec 11.
• [16] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [17] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [18] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [19] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [20] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [21] Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009 Aug 21;138(4):645-659. doi: 10.1016/j.cell.2009.06.034. Epub 2009 Aug 13.
• [22] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [23] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [24] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [25] 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.
• [26] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [27] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [28] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.