Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSS40SS)

• DOT Name: Transcription factor SOX-4 (SOX4)
• Gene Name: SOX4
• Related Disease:
  Adenocarcinoma
  Advanced cancer
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Carcinoma of esophagus
  Clear cell renal carcinoma
  Coffin-Siris syndrome 10
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Constipation
  Endometrial cancer
  Endometrial carcinoma
  Epithelial ovarian cancer
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Intellectual disability
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Medulloblastoma
  Metastatic malignant neoplasm
  Neoplasm
  Neoplasm of esophagus
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Prostate cancer
  Prostate carcinoma
  Squamous cell carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Ventricular septal defect
  Gastric cancer
  Coffin-Siris syndrome
  Melanoma
  Cardiac failure
  Congestive heart failure
  Pancreatic cancer
  Renal cell carcinoma
  Stomach cancer
  Triple negative breast cancer
• UniProt ID: SOX4_HUMAN
• Pfam ID: PF00505
• Sequence:
  MVQQTNNAENTEALLAGESSDSGAGLELGIASSPTPGSTASTGGKADDPSWCKTPSGHIK
  RPMNAFMVWSQIERRKIMEQSPDMHNAEISKRLGKRWKLLKDSDKIPFIREAERLRLKHM
  ADYPDYKYRPRKKVKSGNANSSSSAAASSKPGEKGDKVGGSGGGGHGGGGGGGSSNAGGG
  GGGASGGGANSKPAQKKSCGSKVAGGAGGGVSKPHAKLILAGGGGGGKAAAAAAASFAAE
  QAGAAALLPLGAAADHHSLYKARTPSASASASSAASASAALAAPGKHLAEKKVKRVYLFG
  GLGTSSSPVGGVGAGADPSDPLGLYEEEGAGCSPDAPSLSGRSSAASSPAAGRSPADHRG
  YASLRAASPAPSSAPSHASSSASSHSSSSSSSGSSSSDDEFEDDLLDLNPSSNFESMSLG
  SFSSSSALDRDLDFNFEPGSGSHFEFPDYCTPEVSEMISGDWLESSISNLVFTY
• Function: Transcriptional activator that binds with high affinity to the T-cell enhancer motif 5'-AACAAAG-3' motif. Required for IL17A-producing Vgamma2-positive gamma-delta T-cell maturation and development, via binding to regulator loci of RORC to modulate expression. Involved in skeletal myoblast differentiation by promoting gene expression of CALD1.
• Tissue Specificity: Testis, brain, and heart.
• KEGG Pathway: MicroR.s in cancer (hsa05206)
• Reactome Pathway: Deactivation of the beta-catenin transactivating complex (R-HSA-3769402)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Bladder cancer	DISUHNM0	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[5]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[6]
Coffin-Siris syndrome 10	DIS0CKAH	Strong	Autosomal dominant	[7]
Colon cancer	DISVC52G	Strong	Biomarker	[8]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
Constipation	DISRQXWI	Strong	Genetic Variation	[10]
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[11]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[11]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[12]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[5]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[13]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[14]
Glioma	DIS5RPEH	Strong	Biomarker	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[16]
Intellectual disability	DISMBNXP	Strong	Biomarker	[10]
Lung cancer	DISCM4YA	Strong	Biomarker	[17]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[18]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[19]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[20]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[21]
Neoplasm	DISZKGEW	Strong	Altered Expression	[22]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[5]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[23]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[24]
Prostate cancer	DISF190Y	Strong	Biomarker	[25]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[25]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[26]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[3]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[3]
Ventricular septal defect	DISICO41	Strong	Genetic Variation	[10]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[27]
Coffin-Siris syndrome	DIS8L03H	Supportive	Autosomal dominant	[28]
Melanoma	DIS1RRCY	Disputed	Altered Expression	[29]
Cardiac failure	DISDC067	Limited	Biomarker	[30]
Congestive heart failure	DIS32MEA	Limited	Biomarker	[30]
Pancreatic cancer	DISJC981	Limited	Genetic Variation	[31]
Renal cell carcinoma	DISQZ2X8	Limited	Biomarker	[6]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[27]
Triple negative breast cancer	DISAMG6N	Limited	Altered Expression	[32]

4 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 Transcription factor SOX-4 (SOX4).	[33]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin increases the methylation of Transcription factor SOX-4 (SOX4).	[59]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Transcription factor SOX-4 (SOX4).	[60]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Transcription factor SOX-4 (SOX4).	[63]

37 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 Transcription factor SOX-4 (SOX4).	[34]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription factor SOX-4 (SOX4).	[35]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transcription factor SOX-4 (SOX4).	[36]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription factor SOX-4 (SOX4).	[37]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transcription factor SOX-4 (SOX4).	[38]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transcription factor SOX-4 (SOX4).	[39]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transcription factor SOX-4 (SOX4).	[40]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Transcription factor SOX-4 (SOX4).	[41]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Transcription factor SOX-4 (SOX4).	[42]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Transcription factor SOX-4 (SOX4).	[43]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Transcription factor SOX-4 (SOX4).	[44]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Transcription factor SOX-4 (SOX4).	[45]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Transcription factor SOX-4 (SOX4).	[46]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Transcription factor SOX-4 (SOX4).	[47]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Transcription factor SOX-4 (SOX4).	[48]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Transcription factor SOX-4 (SOX4).	[49]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Transcription factor SOX-4 (SOX4).	[50]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Transcription factor SOX-4 (SOX4).	[51]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Transcription factor SOX-4 (SOX4).	[52]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Transcription factor SOX-4 (SOX4).	[53]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Transcription factor SOX-4 (SOX4).	[54]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Transcription factor SOX-4 (SOX4).	[55]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Transcription factor SOX-4 (SOX4).	[56]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate decreases the expression of Transcription factor SOX-4 (SOX4).	[57]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Transcription factor SOX-4 (SOX4).	[58]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Transcription factor SOX-4 (SOX4).	[40]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Transcription factor SOX-4 (SOX4).	[48]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transcription factor SOX-4 (SOX4).	[61]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Transcription factor SOX-4 (SOX4).	[62]
Celastrol	DMWQIJX	Preclinical	Celastrol decreases the expression of Transcription factor SOX-4 (SOX4).	[64]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transcription factor SOX-4 (SOX4).	[40]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Transcription factor SOX-4 (SOX4).	[58]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Transcription factor SOX-4 (SOX4).	[65]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Transcription factor SOX-4 (SOX4).	[66]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Transcription factor SOX-4 (SOX4).	[67]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Transcription factor SOX-4 (SOX4).	[68]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Transcription factor SOX-4 (SOX4).	[69]

References

• [1] SOX4 interacts with EZH2 and HDAC3 to suppress microRNA-31 in invasive esophageal cancer cells.Mol Cancer. 2015 Feb 3;14:24. doi: 10.1186/s12943-014-0284-y.
• [2] The positive feedback loop of lncRNA DANCR/miR-138/Sox4 facilitates malignancy in non-small cell lung cancer.Am J Cancer Res. 2019 Feb 1;9(2):270-284. eCollection 2019.
• [3] SOX4 regulates invasion of bladder cancer cells via repression of WNT5a.Int J Oncol. 2019 Aug;55(2):359-370. doi: 10.3892/ijo.2019.4832. Epub 2019 Jun 26.
• [4] Long noncoding RNA HOXD-AS1 induces epithelial-mesenchymal transition in breast cancer by acting as a competing endogenous RNA of miR-421.J Cell Biochem. 2019 Jun;120(6):10633-10642. doi: 10.1002/jcb.28353. Epub 2019 Feb 7.
• [5] lncRNA-UCA1 enhances cell proliferation through functioning as a ceRNA of Sox4 in esophageal cancer.Oncol Rep. 2016 Nov;36(5):2960-2966. doi: 10.3892/or.2016.5121. Epub 2016 Sep 22.
• [6] UCA1 promotes cell proliferation and invasion and inhibits apoptosis through regulation of the miR129-SOX4 pathway in renal cell carcinoma.Onco Targets Ther. 2018 May 1;11:2475-2487. doi: 10.2147/OTT.S160192. eCollection 2018.
• [7] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [8] A TGF--MTA1-SOX4-EZH2 signaling axis drives epithelial-mesenchymal transition in tumor metastasis.Oncogene. 2020 Mar;39(10):2125-2139. doi: 10.1038/s41388-019-1132-8. Epub 2019 Dec 6.
• [9] miR-140-5p inhibits cell proliferation and invasion in colorectal carcinoma by targeting SOX4.Oncol Lett. 2019 Feb;17(2):2215-2220. doi: 10.3892/ol.2018.9834. Epub 2018 Dec 14.
• [10] De Novo SOX4 Variants Cause a Neurodevelopmental Disease Associated with Mild Dysmorphism. Am J Hum Genet. 2019 Feb 7;104(2):246-259. doi: 10.1016/j.ajhg.2018.12.014. Epub 2019 Jan 17.
• [11] SOX11 hypermethylation as a tumor biomarker in endometrial cancer.Biochimie. 2019 Jul;162:8-14. doi: 10.1016/j.biochi.2019.03.019. Epub 2019 Mar 29.
• [12] LncRNA SNHG12 accelerates the progression of ovarian cancer via absorbing miRNA-129 to upregulate SOX4.Eur Rev Med Pharmacol Sci. 2019 Mar;23(6):2345-2352. doi: 10.26355/eurrev_201903_17378.
• [13] Propofol Suppresses Esophageal Squamous Cell Carcinoma Cell Migration and Invasion by Down-Regulation of Sex-Determining Region Y-box 4 (SOX4).Med Sci Monit. 2017 Jan 24;23:419-427. doi: 10.12659/msm.899732.
• [14] MicroRNA-29a activates a multi-component growth and invasion program in glioblastoma.J Exp Clin Cancer Res. 2019 Jan 25;38(1):36. doi: 10.1186/s13046-019-1026-1.
• [15] FHL3 links cell growth and self-renewal by modulating SOX4 in glioma.Cell Death Differ. 2019 May;26(5):796-811. doi: 10.1038/s41418-018-0152-1. Epub 2018 Jun 28.
• [16] The Long Noncoding RNA LINC00908 Facilitates Hepatocellular Carcinoma Progression Via Interaction With Sox-4.Cancer Manag Res. 2019 Sep 30;11:8789-8797. doi: 10.2147/CMAR.S216774. eCollection 2019.
• [17] Down-regulated SOX4 expression suppresses cell proliferation, metastasis and induces apoptosis in Xuanwei female lung cancer patients.J Cell Biochem. 2015 Jun;116(6):1007-18. doi: 10.1002/jcb.25055.
• [18] SOX4, an epithelial-mesenchymal transition inducer, transactivates ADAM28 gene expression and co-localizes with ADAM28 at the invasive front of human breast and lung carcinomas.Pathol Int. 2018 Jun 7. doi: 10.1111/pin.12685. Online ahead of print.
• [19] Novel transcriptional targets of the SRY-HMG box transcription factor SOX4 link its expression to the development of small cell lung cancer.Cancer Res. 2012 Jan 1;72(1):176-86. doi: 10.1158/0008-5472.CAN-11-3506. Epub 2011 Nov 14.
• [20] Differential expression and prognostic significance of SOX genes in pediatric medulloblastoma and ependymoma identified by microarray analysis.Neuro Oncol. 2008 Oct;10(5):648-60. doi: 10.1215/15228517-2008-032. Epub 2008 Jun 24.
• [21] LncSOX4 serves an oncogenic role in the tumorigenesis of epithelial ovarian cancer by promoting cell proliferation and inhibiting apoptosis.Mol Med Rep. 2018 Jun;17(6):8282-8288. doi: 10.3892/mmr.2018.8892. Epub 2018 Apr 18.
• [22] miR-138 mediates sorafenib-induced cell survival and is associated with poor prognosis in cholangiocarcinoma cells.Clin Exp Pharmacol Physiol. 2020 Mar;47(3):459-465. doi: 10.1111/1440-1681.13205. Epub 2019 Nov 25.
• [23] SOX4 Allows Facultative -Cell Proliferation Through Repression of Cdkn1a.Diabetes. 2017 Aug;66(8):2213-2219. doi: 10.2337/db16-1074. Epub 2017 May 11.
• [24] miR-363-3p inhibits migration, invasion, and epithelial-mesenchymal transition by targeting NEDD9 and SOX4 in non-small-cell lung cancer.J Cell Physiol. 2020 Feb;235(2):1808-1820. doi: 10.1002/jcp.29099. Epub 2019 Jul 22.
• [25] MicroRNA-140 inhibits proliferation and promotes apoptosis and cell cycle arrest of prostate cancer via degrading SOX4.J BUON. 2019 Jan-Feb;24(1):249-255.
• [26] MicroRNA?99a?p suppresses migration and invasion in oral squamous cell carcinoma through inhibiting the EMTrelated transcription factor SOX4.Int J Mol Med. 2019 Jul;44(1):185-195. doi: 10.3892/ijmm.2019.4174. Epub 2019 Apr 25.
• [27] Circular RNA circ-DONSON facilitates gastric cancer growth and invasion via NURF complex dependent activation of transcription factor SOX4.Mol Cancer. 2019 Mar 28;18(1):45. doi: 10.1186/s12943-019-1006-2.
• [28] Extremely Low Prevalence of Takotsubo Cardiomyopathy and Transient Cardiac Dysfunction in Stroke Patients With T-wave Abnormalities. Am J Cardiol. 2019 Mar 15;123(6):1009. doi: 10.1016/j.amjcard.2019.01.001. Epub 2019 Jan 9.
• [29] miR?0a?p inhibits the proliferation, migration and invasion of melanoma cells by targeting SOX4.Mol Med Rep. 2018 Aug;18(2):2492-2498. doi: 10.3892/mmr.2018.9166. Epub 2018 Jun 14.
• [30] A context-specific cardiac -catenin and GATA4 interaction influences TCF7L2 occupancy and remodels chromatin driving disease progression in the adult heart.Nucleic Acids Res. 2018 Apr 6;46(6):2850-2867. doi: 10.1093/nar/gky049.
• [31] Transcriptome-wide association study identifies multiple genes and pathways associated with pancreatic cancer.Cancer Med. 2018 Nov;7(11):5727-5732. doi: 10.1002/cam4.1836. Epub 2018 Oct 18.
• [32] An androgen receptor negatively induced long non-coding RNA ARNILA binding to miR-204 promotes the invasion and metastasis of triple-negative breast cancer.Cell Death Differ. 2018 Dec;25(12):2209-2220. doi: 10.1038/s41418-018-0123-6. Epub 2018 May 29.
• [33] 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.
• [34] 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.
• [35] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [36] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [37] 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.
• [38] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [39] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [40] Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
• [41] 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.
• [42] 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.
• [43] Changes in gene expression profiles of multiple myeloma cells induced by arsenic trioxide (ATO): possible mechanisms to explain ATO resistance in vivo. Br J Haematol. 2005 Mar;128(5):636-44.
• [44] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [45] 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.
• [46] 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.
• [47] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [48] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [49] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [50] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [51] High folic acid increases cell turnover and lowers differentiation and iron content in human HT29 colon cancer cells. Br J Nutr. 2008 Apr;99(4):703-8.
• [52] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [53] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [54] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [55] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [56] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [57] Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial epithelial cell line demonstrates a major influence on heat-shock proteins. Physiol Genomics. 2004 Jan 15;16(2):204-11.
• [58] 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.
• [59] Reduced camptothecin sensitivity of estrogen receptor-positive human breast cancer cells following exposure to di(2-ethylhexyl)phthalate (DEHP) is associated with DNA methylation changes. Environ Toxicol. 2019 Apr;34(4):401-414.
• [60] 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.
• [61] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [62] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [63] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [64] Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell. 2006 Oct;10(4):321-30.
• [65] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [66] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [67] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [68] 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.
• [69] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.