Details of Drug Off-Target (DOT)

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

• DOT Name: ETS-related transcription factor Elf-3 (ELF3)
• Synonyms: E74-like factor 3; Epithelial-restricted with serine box; Epithelium-restricted Ets protein ESX; Epithelium-specific Ets transcription factor 1; ESE-1
• Gene Name: ELF3
• Related Disease:
  Colorectal carcinoma
  Endometrial cancer
  Endometrial carcinoma
  Metastatic malignant neoplasm
  Squamous cell carcinoma
  Tuberculosis
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colitis
  Diabetic kidney disease
  Epithelial ovarian cancer
  Gastric cancer
  Glycogen storage disease type II
  Head-neck squamous cell carcinoma
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Lysosomal storage disease
  Neoplasm
  Osteoarthritis
  Ovarian cancer
  Ovarian neoplasm
  Rheumatoid arthritis
  Stomach cancer
  Synovial sarcoma
  Thyroid gland papillary carcinoma
  Ulcerative colitis
  Bladder cancer
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Urinary bladder cancer
  Urinary bladder neoplasm
  Adenocarcinoma
  Acute lymphocytic leukaemia
  Acute myelogenous leukaemia
  Biliary tract cancer
  Biliary tract neoplasm
  Glycogen storage disease due to acid maltase deficiency, late-onset
  Hepatocellular carcinoma
  Hyperlipidemia
  Lymphoma
  Nasopharyngeal carcinoma
  Non-small-cell lung cancer
  Thrombophilia
  Type-1 diabetes
• UniProt ID: ELF3_HUMAN
• PDB ID: 2E8P
• Pfam ID: PF00178 ; PF02198
• Sequence:
  MAATCEISNIFSNYFSAMYSSEDSTLASVPPAATFGADDLVLTLSNPQMSLEGTEKASWL
  GEQPQFWSKTQVLDWISYQVEKNKYDASAIDFSRCDMDGATLCNCALEELRLVFGPLGDQ
  LHAQLRDLTSSSSDELSWIIELLEKDGMAFQEALDPGPFDQGSPFAQELLDDGQQASPYH
  PGSCGAGAPSPGSSDVSTAGTGASRSSHSSDSGGSDVDLDPTDGKLFPSDGFRDCKKGDP
  KHGKRKRGRPRKLSKEYWDCLEGKKSKHAPRGTHLWEFIRDILIHPELNEGLMKWENRHE
  GVFKFLRSEAVAQLWGQKKKNSNMTYEKLSRAMRYYYKREILERVDGRRLVYKFGKNSSG
  WKEEEVLQSRN
• Function: Transcriptional activator that binds and transactivates ETS sequences containing the consensus nucleotide core sequence GGA[AT]. Acts synergistically with POU2F3 to transactivate the SPRR2A promoter and with RUNX1 to transactivate the ANGPT1 promoter. Also transactivates collagenase, CCL20, CLND7, FLG, KRT8, NOS2, PTGS2, SPRR2B, TGFBR2 and TGM3 promoters. Represses KRT4 promoter activity. Involved in mediating vascular inflammation. May play an important role in epithelial cell differentiation and tumorigenesis. May be a critical downstream effector of the ERBB2 signaling pathway. May be associated with mammary gland development and involution. Plays an important role in the regulation of transcription with TATA-less promoters in preimplantation embryos, which is essential in preimplantation development.
• Tissue Specificity: Expressed exclusively in tissues containing a high content of terminally differentiated epithelial cells including mammary gland, colon, trachea, kidney, prostate, uterus, stomach and skin.
• Reactome Pathway: Pre-NOTCH Transcription and Translation (R-HSA-1912408)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Definitive	Altered Expression	[1]
Endometrial cancer	DISW0LMR	Definitive	Biomarker	[2]
Endometrial carcinoma	DISXR5CY	Definitive	Biomarker	[2]
Metastatic malignant neoplasm	DIS86UK6	Definitive	Biomarker	[1]
Squamous cell carcinoma	DISQVIFL	Definitive	Biomarker	[3]
Tuberculosis	DIS2YIMD	Definitive	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Colitis	DISAF7DD	Strong	Altered Expression	[8]
Diabetic kidney disease	DISJMWEY	Strong	Altered Expression	[9]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[10]
Gastric cancer	DISXGOUK	Strong	Biomarker	[11]
Glycogen storage disease type II	DISXZPBC	Strong	Biomarker	[12]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[13]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[14]
Lung cancer	DISCM4YA	Strong	Biomarker	[14]
Lung carcinoma	DISTR26C	Strong	Biomarker	[14]
Lysosomal storage disease	DIS6QM6U	Strong	Biomarker	[15]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Osteoarthritis	DIS05URM	Strong	Biomarker	[16]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[10]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[10]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[17]
Stomach cancer	DISKIJSX	Strong	Biomarker	[11]
Synovial sarcoma	DISEZJS7	Strong	Altered Expression	[18]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Altered Expression	[19]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[8]
Bladder cancer	DISUHNM0	moderate	Biomarker	[20]
Prostate cancer	DISF190Y	moderate	Biomarker	[21]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[21]
Prostate neoplasm	DISHDKGQ	moderate	Altered Expression	[21]
Urinary bladder cancer	DISDV4T7	moderate	Biomarker	[20]
Urinary bladder neoplasm	DIS7HACE	moderate	Biomarker	[20]
Adenocarcinoma	DIS3IHTY	Disputed	Biomarker	[14]
Acute lymphocytic leukaemia	DISPX75S	Limited	Altered Expression	[22]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[23]
Biliary tract cancer	DISBNYQL	Limited	Biomarker	[24]
Biliary tract neoplasm	DISLWLHH	Limited	Biomarker	[24]
Glycogen storage disease due to acid maltase deficiency, late-onset	DISKE80D	Limited	Genetic Variation	[25]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[26]
Hyperlipidemia	DIS61J3S	Limited	Genetic Variation	[27]
Lymphoma	DISN6V4S	Limited	Altered Expression	[22]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[28]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[29]
Thrombophilia	DISQR7U7	Limited	Genetic Variation	[27]
Type-1 diabetes	DIS7HLUB	Limited	Altered Expression	[30]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	ETS-related transcription factor Elf-3 (ELF3) decreases the response to substance of Arsenic trioxide.	[61]

3 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 ETS-related transcription factor Elf-3 (ELF3).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of ETS-related transcription factor Elf-3 (ELF3).	[55]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of ETS-related transcription factor Elf-3 (ELF3).	[57]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of ETS-related transcription factor Elf-3 (ELF3).	[32]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of ETS-related transcription factor Elf-3 (ELF3).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of ETS-related transcription factor Elf-3 (ELF3).	[34]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ETS-related transcription factor Elf-3 (ELF3).	[35]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of ETS-related transcription factor Elf-3 (ELF3).	[36]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of ETS-related transcription factor Elf-3 (ELF3).	[37]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of ETS-related transcription factor Elf-3 (ELF3).	[38]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of ETS-related transcription factor Elf-3 (ELF3).	[39]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of ETS-related transcription factor Elf-3 (ELF3).	[40]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of ETS-related transcription factor Elf-3 (ELF3).	[41]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of ETS-related transcription factor Elf-3 (ELF3).	[42]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of ETS-related transcription factor Elf-3 (ELF3).	[43]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of ETS-related transcription factor Elf-3 (ELF3).	[44]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of ETS-related transcription factor Elf-3 (ELF3).	[45]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of ETS-related transcription factor Elf-3 (ELF3).	[46]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of ETS-related transcription factor Elf-3 (ELF3).	[47]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of ETS-related transcription factor Elf-3 (ELF3).	[48]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of ETS-related transcription factor Elf-3 (ELF3).	[49]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of ETS-related transcription factor Elf-3 (ELF3).	[50]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of ETS-related transcription factor Elf-3 (ELF3).	[51]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of ETS-related transcription factor Elf-3 (ELF3).	[43]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of ETS-related transcription factor Elf-3 (ELF3).	[52]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of ETS-related transcription factor Elf-3 (ELF3).	[47]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of ETS-related transcription factor Elf-3 (ELF3).	[53]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of ETS-related transcription factor Elf-3 (ELF3).	[54]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of ETS-related transcription factor Elf-3 (ELF3).	[56]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of ETS-related transcription factor Elf-3 (ELF3).	[58]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of ETS-related transcription factor Elf-3 (ELF3).	[59]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of ETS-related transcription factor Elf-3 (ELF3).	[48]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of ETS-related transcription factor Elf-3 (ELF3).	[60]

References

• [1] Significance of ELF3 mRNA expression for detection of lymph node metastases of colorectal cancer.Anticancer Res. 2012 Sep;32(9):3753-8.
• [2] LVSI positive and NX in early endometrial cancer: Surgical restaging (and no further treatment if N0), or adjuvant ERT?.Gynecol Oncol. 2020 Jan;156(1):243-250. doi: 10.1016/j.ygyno.2019.09.016. Epub 2019 Nov 5.
• [3] Loss of ELF3 immunoexpression is useful for detecting oral squamous cell carcinoma but not for distinguishing between grades of epithelial dysplasia.Ann Diagn Pathol. 2013 Aug;17(4):331-40. doi: 10.1016/j.anndiagpath.2013.03.003. Epub 2013 May 3.
• [4] Biophysical and immunological characterization of the ESX-4 system ESAT-6 family proteins Rv3444c and Rv3445c from Mycobacterium tuberculosis H37Rv.Tuberculosis (Edinb). 2018 Mar;109:85-96. doi: 10.1016/j.tube.2018.02.002. Epub 2018 Feb 13.
• [5] ELF3 is an antagonist of oncogenic-signalling-induced expression of EMT-TF ZEB1.Cancer Biol Ther. 2019;20(1):90-100. doi: 10.1080/15384047.2018.1507256. Epub 2018 Aug 27.
• [6] ESE-1 Knockdown Attenuates Growth in Trastuzumab-resistant HER2(+) Breast Cancer Cells.Anticancer Res. 2017 Dec;37(12):6583-6591. doi: 10.21873/anticanres.12115.
• [7] Function of PEA3 Ets transcription factors in mammary gland development and oncogenesis.J Mammary Gland Biol Neoplasia. 2003 Apr;8(2):177-90. doi: 10.1023/a:1025948823955.
• [8] Epithelial-specific ETS-1 (ESE1/ELF3) regulates apoptosis of intestinal epithelial cells in ulcerative colitis via accelerating NF-B activation.Immunol Res. 2015 Jun;62(2):198-212. doi: 10.1007/s12026-015-8651-3.
• [9] Involvement of Elf3 on Smad3 activation-dependent injuries in podocytes and excretion of urinary exosome in diabetic nephropathy.PLoS One. 2019 May 31;14(5):e0216788. doi: 10.1371/journal.pone.0216788. eCollection 2019.
• [10] ELF3 is a negative regulator of epithelial-mesenchymal transition in ovarian cancer cells.Oncotarget. 2017 Mar 7;8(10):16951-16963. doi: 10.18632/oncotarget.15208.
• [11] IRF6 Is Directly Regulated by ZEB1 and ELF3, and Predicts a Favorable Prognosis in Gastric Cancer.Front Oncol. 2019 Apr 4;9:220. doi: 10.3389/fonc.2019.00220. eCollection 2019.
• [12] Evaluation of antihypertensive drugs in combination with enzyme replacement therapy in mice with Pompe disease.Mol Genet Metab. 2020 Feb;129(2):73-79. doi: 10.1016/j.ymgme.2019.10.005. Epub 2019 Oct 17.
• [13] miR-124 Regulates the Epithelial-Restricted with Serine Box/Epidermal Growth Factor Receptor Signaling Axis in Head and Neck Squamous Cell Carcinoma.Mol Cancer Ther. 2015 Oct;14(10):2313-20. doi: 10.1158/1535-7163.MCT-14-1071. Epub 2015 Jul 30.
• [14] Epithelial tumor suppressor ELF3 is a lineage-specific amplified oncogene in lung adenocarcinoma.Nat Commun. 2019 Nov 28;10(1):5438. doi: 10.1038/s41467-019-13295-y.
• [15] Human recombinant lysosomal enzymes produced in microorganisms.Mol Genet Metab. 2015 Sep-Oct;116(1-2):13-23. doi: 10.1016/j.ymgme.2015.06.001. Epub 2015 Jun 6.
• [16] Elf3 Contributes to Cartilage Degradation in vivo in a Surgical Model of Post-Traumatic Osteoarthritis.Sci Rep. 2018 Apr 24;8(1):6438. doi: 10.1038/s41598-018-24695-3.
• [17] ESE-1 is a novel transcriptional mediator of angiopoietin-1 expression in the setting of inflammation.J Biol Chem. 2004 Mar 26;279(13):12794-803. doi: 10.1074/jbc.M308593200. Epub 2004 Jan 8.
• [18] Expression of claudin7 is tightly associated with epithelial structures in synovial sarcomas and regulated by an Ets family transcription factor, ELF3.J Biol Chem. 2006 Dec 15;281(50):38941-50. doi: 10.1074/jbc.M608389200. Epub 2006 Oct 23.
• [19] E26 transformation (ETS)specific related transcription factor? (ELF3) orchestrates a positive feedback loop that constitutively activates the MAPK/Erk pathway to drive thyroid cancer.Oncol Rep. 2019 Jan;41(1):570-578. doi: 10.3892/or.2018.6807. Epub 2018 Oct 18.
• [20] E74 like ETS transcription factor 3 (ELF3) is a negative regulator of epithelial- mesenchymal transition in bladder carcinoma.Cancer Biomark. 2019;25(2):223-232. doi: 10.3233/CBM-190013.
• [21] ETS transcription factor ESE1/ELF3 orchestrates a positive feedback loop that constitutively activates NF-B and drives prostate cancer progression.Cancer Res. 2013 Jul 15;73(14):4533-47. doi: 10.1158/0008-5472.CAN-12-4537. Epub 2013 May 16.
• [22] Disturbed expression of the anti-apoptosis gene, survivin, and EPR-1 in hematological malignancies.Leuk Res. 2000 Nov;24(11):965-70. doi: 10.1016/s0145-2126(00)00065-5.
• [23] Ezh2 augments leukemogenicity by reinforcing differentiation blockage in acute myeloid leukemia.Blood. 2012 Aug 2;120(5):1107-17. doi: 10.1182/blood-2011-11-394932. Epub 2012 Jun 7.
• [24] Genomic spectra of biliary tract cancer.Nat Genet. 2015 Sep;47(9):1003-10. doi: 10.1038/ng.3375. Epub 2015 Aug 10.
• [25] Correction of Biochemical Abnormalities and Improved Muscle Function in a Phase I/II Clinical Trial of Clenbuterol in Pompe Disease.Mol Ther. 2018 Sep 5;26(9):2304-2314. doi: 10.1016/j.ymthe.2018.06.023. Epub 2018 Jul 5.
• [26] ELF3 promotes epithelial-mesenchymal transition by protecting ZEB1 from miR-141-3p-mediated silencing in hepatocellular carcinoma.Cell Death Dis. 2018 Mar 9;9(3):387. doi: 10.1038/s41419-018-0399-y.
• [27] Estrogen replacement therapy, thrombophilia, and atherothrombosis.Metabolism. 2002 Jun;51(6):724-32. doi: 10.1053/meta.2002.32729.
• [28] CircHIPK3 promotes proliferation and invasion in nasopharyngeal carcinoma by abrogating miR-4288-induced ELF3 inhibition.J Cell Physiol. 2019 Feb;234(2):1699-1706. doi: 10.1002/jcp.27041. Epub 2018 Aug 2.
• [29] Overexpression of ELF3 facilitates cell growth and metastasis through PI3K/Akt and ERK signaling pathways in non-small cell lung cancer.Int J Biochem Cell Biol. 2018 Jan;94:98-106. doi: 10.1016/j.biocel.2017.12.002. Epub 2017 Dec 5.
• [30] Temporal profiling of cytokine-induced genes in pancreatic -cells by meta-analysis and network inference.Genomics. 2014 Apr;103(4):264-75. doi: 10.1016/j.ygeno.2013.12.007. Epub 2014 Jan 24.
• [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] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [38] Analysis of estrogen agonism and antagonism of tamoxifen, raloxifene, and ICI182780 in endometrial cancer cells: a putative role for the epidermal growth factor receptor ligand amphiregulin. J Soc Gynecol Investig. 2005 Oct;12(7):e55-67.
• [39] 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.
• [40] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [41] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [42] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [43] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [44] 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.
• [45] 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.
• [46] Progestins regulate genes that can elicit both proliferative and antiproliferative effects in breast cancer cells. Oncol Rep. 2008 Jun;19(6):1627-34.
• [47] 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.
• [48] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [49] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [50] In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Toxicol In Vitro. 2013 Apr;27(3):1072-81.
• [51] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [52] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [53] Regulation of lipocalin-2 gene by the cancer chemopreventive retinoid 4-HPR. Int J Cancer. 2006 Oct 1;119(7):1599-606.
• [54] Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. Cancer Res. 2006 Jul 15;66(14):7334-40.
• [55] 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.
• [56] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [57] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [58] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [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] 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.
• [61] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.