Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU2NUA2)

• DOT Name: Ephrin-A1 (EFNA1)
• Synonyms: EPH-related receptor tyrosine kinase ligand 1; LERK-1; Immediate early response protein B61; Tumor necrosis factor alpha-induced protein 4; TNF alpha-induced protein 4
• Gene Name: EFNA1
• Related Disease:
  HER2/NEU overexpressing breast cancer
  Acute myocardial infarction
  Bladder cancer
  Bone osteosarcoma
  Breast neoplasm
  Clear cell renal carcinoma
  Colon carcinoma
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Gastric cancer
  Giant cell tumor
  Glioma
  Hepatocellular carcinoma
  Intestinal neoplasm
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Malignant pleural mesothelioma
  Melanoma
  Neoplasm
  Non-small-cell lung cancer
  Osteosarcoma
  Ovarian cancer
  Ovarian neoplasm
  Pre-eclampsia
  Pulmonary arterial hypertension
  Stomach cancer
  Transitional cell carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Urothelial carcinoma
  Squamous cell carcinoma
  Gastric neoplasm
  Metastatic malignant neoplasm
  Adenocarcinoma
  Advanced cancer
  Asthma
  Carcinoma
  Colorectal carcinoma
  Congenital contractural arachnodactyly
  Diabetic kidney disease
  Type-1 diabetes
• UniProt ID: EFNA1_HUMAN
• PDB ID: 3CZU; 3HEI; 3MBW
• Pfam ID: PF00812
• Sequence:
  MEFLWAPLLGLCCSLAAADRHTVFWNSSNPKFRNEDYTIHVQLNDYVDIICPHYEDHSVA
  DAAMEQYILYLVEHEEYQLCQPQSKDQVRWQCNRPSAKHGPEKLSEKFQRFTPFTLGKEF
  KEGHSYYYISKPIHQHEDRCLRLKVTVSGKITHSPQAHDNPQEKRLAADDPEVRVLHSIG
  HSAAPRLFPLAWTVLLLPLLLLQTP
• Function: Cell surface GPI-bound ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. Plays an important role in angiogenesis and tumor neovascularization. The recruitment of VAV2, VAV3 and PI3-kinase p85 subunit by phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly. Exerts anti-oncogenic effects in tumor cells through activation and down-regulation of EPHA2. Activates EPHA2 by inducing tyrosine phosphorylation which leads to its internalization and degradation. Acts as a negative regulator in the tumorigenesis of gliomas by down-regulating EPHA2 and FAK. Can evoke collapse of embryonic neuronal growth cone and regulates dendritic spine morphogenesis.
• Tissue Specificity: Brain. Down-regulated in primary glioma tissues compared to the normal tissues. The soluble monomeric form is expressed in the glioblastoma multiforme (GBM) and breast cancer cells (at protein level).
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  Ras sig.ling pathway (hsa04014)
  Rap1 sig.ling pathway (hsa04015)
  PI3K-Akt sig.ling pathway (hsa04151)
  Axon guidance (hsa04360)
  MicroR.s in cancer (hsa05206)
• Reactome Pathway:
  EPHA-mediated growth cone collapse (R-HSA-3928663)
  EPH-ephrin mediated repulsion of cells (R-HSA-3928665)
  EPH-Ephrin signaling (R-HSA-2682334)

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
HER2/NEU overexpressing breast cancer	DISYKID5	Definitive	Biomarker	[1]
Acute myocardial infarction	DISE3HTG	Strong	Altered Expression	[2]
Bladder cancer	DISUHNM0	Strong	Biomarker	[3]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[5]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[6]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[7]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[8]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[9]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[10]
Giant cell tumor	DIS8LOIN	Strong	Altered Expression	[11]
Glioma	DIS5RPEH	Strong	Biomarker	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[13]
Intestinal neoplasm	DISK0GUH	Strong	Biomarker	[14]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[15]
Lung cancer	DISCM4YA	Strong	Biomarker	[16]
Lung carcinoma	DISTR26C	Strong	Biomarker	[16]
Malignant pleural mesothelioma	DIST2R60	Strong	Biomarker	[16]
Melanoma	DIS1RRCY	Strong	Biomarker	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[18]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[19]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[4]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[8]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[8]
Pre-eclampsia	DISY7Q29	Strong	Altered Expression	[20]
Pulmonary arterial hypertension	DISP8ZX5	Strong	Altered Expression	[21]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[10]
Transitional cell carcinoma	DISWVVDR	Strong	Biomarker	[22]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[3]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[3]
Urothelial carcinoma	DISRTNTN	Strong	Biomarker	[22]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[23]
Gastric neoplasm	DISOKN4Y	Disputed	Altered Expression	[24]
Metastatic malignant neoplasm	DIS86UK6	Disputed	Altered Expression	[25]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[26]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[18]
Asthma	DISW9QNS	Limited	Altered Expression	[27]
Carcinoma	DISH9F1N	Limited	Altered Expression	[26]
Colorectal carcinoma	DIS5PYL0	Limited	Genetic Variation	[28]
Congenital contractural arachnodactyly	DISOM1K7	Limited	Biomarker	[29]
Diabetic kidney disease	DISJMWEY	Limited	Biomarker	[30]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Ephrin-A1 (EFNA1).	[31]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ephrin-A1 (EFNA1).	[32]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ephrin-A1 (EFNA1).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ephrin-A1 (EFNA1).	[34]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ephrin-A1 (EFNA1).	[35]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ephrin-A1 (EFNA1).	[36]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ephrin-A1 (EFNA1).	[37]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ephrin-A1 (EFNA1).	[38]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ephrin-A1 (EFNA1).	[40]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Ephrin-A1 (EFNA1).	[41]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Ephrin-A1 (EFNA1).	[42]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Ephrin-A1 (EFNA1).	[43]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Ephrin-A1 (EFNA1).	[44]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Ephrin-A1 (EFNA1).	[45]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Ephrin-A1 (EFNA1).	[46]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Ephrin-A1 (EFNA1).	[47]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Ephrin-A1 (EFNA1).	[48]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Ephrin-A1 (EFNA1).	[49]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Ephrin-A1 (EFNA1).	[45]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Ephrin-A1 (EFNA1).	[38]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Ephrin-A1 (EFNA1).	[50]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Ephrin-A1 (EFNA1).	[51]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Ephrin-A1 (EFNA1).	[52]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Ephrin-A1 (EFNA1).	[53]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Ephrin-A1 (EFNA1).	[54]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of Ephrin-A1 (EFNA1).	[37]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of Ephrin-A1 (EFNA1).	[37]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Ephrin-A1 (EFNA1).	[37]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil decreases the expression of Ephrin-A1 (EFNA1).	[37]
Estrone	DM5T6US	Approved	Estrone decreases the expression of Ephrin-A1 (EFNA1).	[52]
Mestranol	DMG3F94	Approved	Mestranol decreases the expression of Ephrin-A1 (EFNA1).	[52]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ephrin-A1 (EFNA1).	[45]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Ephrin-A1 (EFNA1).	[52]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Ephrin-A1 (EFNA1).	[45]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Ephrin-A1 (EFNA1).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ephrin-A1 (EFNA1).	[55]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Ephrin-A1 (EFNA1).	[56]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ephrin-A1 (EFNA1).	[57]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ephrin-A1 (EFNA1).	[58]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ephrin-A1 (EFNA1).	[59]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Ephrin-A1 (EFNA1).	[60]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Ephrin-A1 (EFNA1).	[61]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Ephrin-A1 (EFNA1).	[62]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Ephrin-A1 (EFNA1).	[58]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Ephrin-A1 (EFNA1).	[63]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the methylation of Ephrin-A1 (EFNA1).	[39]

References

• [1] The Ephrin-A1/EPHA2 Signaling Axis Regulates Glutamine Metabolism in HER2-Positive Breast Cancer.Cancer Res. 2016 Apr 1;76(7):1825-36. doi: 10.1158/0008-5472.CAN-15-0847. Epub 2016 Feb 1.
• [2] The ephrin A1-EphA2 system promotes cardiac stem cell migration after infarction.Circ Res. 2011 Apr 29;108(9):1071-83. doi: 10.1161/CIRCRESAHA.110.239459. Epub 2011 Mar 17.
• [3] Inhibition of angiogenesis by leflunomide via targeting the soluble ephrin-A1/EphA2 system in bladder cancer.Sci Rep. 2018 Jan 24;8(1):1539. doi: 10.1038/s41598-018-19788-y.
• [4] De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway.Histopathology. 2010 Dec;57(6):836-50. doi: 10.1111/j.1365-2559.2010.03713.x.
• [5] A potential tumor suppressor role for Hic1 in breast cancer through transcriptional repression of ephrin-A1.Oncogene. 2010 Apr 29;29(17):2467-76. doi: 10.1038/onc.2010.12. Epub 2010 Feb 15.
• [6] Lack of ephrin receptor A1 is a favorable independent prognostic factor in clear cell renal cell carcinoma.PLoS One. 2014 Jul 15;9(7):e102262. doi: 10.1371/journal.pone.0102262. eCollection 2014.
• [7] Reduced expression of EphrinA1 (EFNA1) inhibits three-dimensional growth of HT29 colon carcinoma cells.Cancer Lett. 2002 Jan 25;175(2):187-95. doi: 10.1016/s0304-3835(01)00613-9.
• [8] Knockdown of EPHA1 Using CRISPR/CAS9 Suppresses Aggressive Properties of Ovarian Cancer Cells.Anticancer Res. 2017 Aug;37(8):4415-4424. doi: 10.21873/anticanres.11836.
• [9] The effect of ephrin-A1 on resistance to Photofrin-mediated photodynamic therapy in esophageal squamous cell carcinoma cells.Lasers Med Sci. 2015 Dec;30(9):2353-61. doi: 10.1007/s10103-015-1812-8. Epub 2015 Oct 8.
• [10] G-A variant in miR-200c binding site of EFNA1 alters susceptibility to gastric cancer.Mol Carcinog. 2014 Mar;53(3):219-29. doi: 10.1002/mc.21966. Epub 2012 Oct 12.
• [11] Giant cell tumors of the bone: molecular profiling and expression analysis of Ephrin A1 receptor, Claudin 7, CD52, FGFR3 and AMFR.Pathol Res Pract. 2005;201(10):649-63. doi: 10.1016/j.prp.2005.07.005. Epub 2005 Sep 26.
• [12] EphA2 mediates ligand-dependent inhibition and ligand-independent promotion of cell migration and invasion via a reciprocal regulatory loop with Akt.Cancer Cell. 2009 Jul 7;16(1):9-20. doi: 10.1016/j.ccr.2009.04.009.
• [13] Role of C-X-C chemokine ligand 12/C-X-C chemokine receptor 4 in the progression of hepatocellular carcinoma.Oncol Lett. 2017 Aug;14(2):1905-1910. doi: 10.3892/ol.2017.6396. Epub 2017 Jun 16.
• [14] Ephrin-A1 promotes the malignant progression of intestinal tumors in Apc(min/+) mice.Oncogene. 2008 May 22;27(23):3265-73. doi: 10.1038/sj.onc.1210992. Epub 2008 Feb 4.
• [15] Global evaluation of Eph receptors and ephrins in lung adenocarcinomas identifies EphA4 as an inhibitor of cell migration and invasion.Mol Cancer Ther. 2012 Sep;11(9):2021-32. doi: 10.1158/1535-7163.MCT-12-0030. Epub 2012 Jul 17.
• [16] Targeted delivery of let-7a microRNA encapsulated ephrin-A1 conjugated liposomal nanoparticles inhibit tumor growth in lung cancer.Int J Nanomedicine. 2013;8:4481-94. doi: 10.2147/IJN.S41782. Epub 2013 Nov 21.
• [17] Up-regulation of ephrin-A1 during melanoma progression.Int J Cancer. 1999 Oct 22;84(5):494-501. doi: 10.1002/(sici)1097-0215(19991022)84:5<494::aid-ijc8>3.0.co;2-o.
• [18] Roles of EphA1/A2 and ephrin-A1 in cancer.Cancer Sci. 2019 Mar;110(3):841-848. doi: 10.1111/cas.13942. Epub 2019 Feb 15.
• [19] Ephrin B3 interacts with multiple EphA receptors and drives migration and invasion in non-small cell lung cancer.Oncotarget. 2016 Sep 13;7(37):60332-60347. doi: 10.18632/oncotarget.11219.
• [20] Eph and ephrin expression in normal placental development and preeclampsia.Placenta. 2004 Aug;25(7):623-30. doi: 10.1016/j.placenta.2004.01.016.
• [21] RNA Sequencing Analysis Detection of a Novel Pathway of Endothelial Dysfunction in Pulmonary Arterial Hypertension.Am J Respir Crit Care Med. 2015 Aug 1;192(3):356-66. doi: 10.1164/rccm.201408-1528OC.
• [22] Expression of EphA2 and Ephrin A-1 in carcinoma of the urinary bladder.Clin Cancer Res. 2006 Jan 15;12(2):353-60. doi: 10.1158/1078-0432.CCR-05-1505.
• [23] Ephrin-A1 is up-regulated by hypoxia in cancer cells and promotes angiogenesis of HUVECs through a coordinated cross-talk with eNOS.PLoS One. 2013 Sep 9;8(9):e74464. doi: 10.1371/journal.pone.0074464. eCollection 2013.
• [24] EPHA2/EFNA1 expression in human gastric cancer.Cancer Sci. 2005 Jan;96(1):42-7. doi: 10.1111/j.1349-7006.2005.00007.x.
• [25] Long Noncoding RNA GMAN, Up-regulated in Gastric Cancer Tissues, Is Associated With Metastasis in Patients and Promotes Translation of Ephrin A1 by Competitively Binding GMAN-AS.Gastroenterology. 2019 Feb;156(3):676-691.e11. doi: 10.1053/j.gastro.2018.10.054. Epub 2018 Nov 13.
• [26] Higher expression of EphA2 and ephrin-A1 is related to favorable clinicopathological features in pathological stage I non-small cell lung carcinoma.Lung Cancer. 2012 Jun;76(3):431-8. doi: 10.1016/j.lungcan.2011.12.004. Epub 2012 Jan 10.
• [27] Ephrin-A1 suppresses Th2 cell activation and provides a regulatory link to lung epithelial cells.J Immunol. 2004 Jan 15;172(2):843-50. doi: 10.4049/jimmunol.172.2.843.
• [28] rs12904 polymorphism in the 3'-untranslated region of ephrin A1 ligand and the risk of sporadic colorectal cancer in the Iranian population.J Cancer Res Ther. 2019 Jan-Mar;15(1):15-19. doi: 10.4103/jcrt.JCRT_766_17.
• [29] Upregulation of endothelial nitric oxide synthase (eNOS) and its upstream regulators in Opisthorchis viverrini associated cholangiocarcinoma and its clinical significance.Parasitol Int. 2017 Aug;66(4):486-493. doi: 10.1016/j.parint.2016.04.008. Epub 2016 Apr 30.
• [30] Genome-wide pathway analysis for diabetic nephropathy in type 1 diabetes.Endocr Res. 2016;41(1):21-7. doi: 10.3109/07435800.2015.1044011. Epub 2015 Jul 13.
• [31] 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.
• [32] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [33] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [34] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [35] 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.
• [36] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [37] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [38] Estrogen regulation in human breast cancer cells of new downstream gene targets involved in estrogen metabolism, cell proliferation and cell transformation. J Mol Endocrinol. 2004 Apr;32(2):397-414.
• [39] Association of Arsenic Exposure with Whole Blood DNA Methylation: An Epigenome-Wide Study of Bangladeshi Adults. Environ Health Perspect. 2019 May;127(5):57011. doi: 10.1289/EHP3849. Epub 2019 May 28.
• [40] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [41] 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.
• [42] 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.
• [43] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [44] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [45] 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.
• [46] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [47] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [48] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [49] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [50] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [51] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [52] Moving toward integrating gene expression profiling into high-throughput testing: a gene expression biomarker accurately predicts estrogen receptor alpha modulation in a microarray compendium. Toxicol Sci. 2016 May;151(1):88-103.
• [53] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [54] 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.
• [55] Gene expression changes associated with altered growth and differentiation in benzo[a]pyrene or arsenic exposed normal human epidermal keratinocytes. J Appl Toxicol. 2008 May;28(4):491-508.
• [56] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [57] 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.
• [58] Evaluation of estrogen receptor alpha activation by glyphosate-based herbicide constituents. Food Chem Toxicol. 2017 Oct;108(Pt A):30-42.
• [59] 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.
• [60] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [61] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [62] 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.
• [63] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.