Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1C9NKQ)

• DOT Name: Retinaldehyde dehydrogenase 3 (ALDH1A3)
• Synonyms: RALDH-3; RalDH3; EC 1.2.1.36; Aldehyde dehydrogenase 6; Aldehyde dehydrogenase family 1 member A3; ALDH1A3
• Gene Name: ALDH1A3
• Related Disease:
  Adenocarcinoma
  HER2/NEU overexpressing breast cancer
  Non-small-cell lung cancer
  Advanced cancer
  Autism spectrum disorder
  Brain cancer
  Brain neoplasm
  Breast cancer
  Breast carcinoma
  Cholangiocarcinoma
  Coloboma
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Colorectal carcinoma
  Congenital contractural arachnodactyly
  Familial adenomatous polyposis
  Fatty liver disease
  Gallbladder cancer
  Glioblastoma multiforme
  Glioma
  Isolated microphthalmia 8
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Malignant glioma
  Melanoma
  Metastatic melanoma
  Neoplasm
  Pancreatic cancer
  Pervasive developmental disorder
  Polycystic ovarian syndrome
  Testicular germ cell tumor
  Breast neoplasm
  Meningioma
  Prostate cancer
  Prostate carcinoma
  Isolated anophthalmia-microphthalmia syndrome
  Adult glioblastoma
  Gastric cancer
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Malignant pleural mesothelioma
  Meckel syndrome, type 1
  Microphthalmia
  Neuroblastoma
  Rheumatoid arthritis
  Triple negative breast cancer
• UniProt ID: AL1A3_HUMAN
• PDB ID: 5FHZ; 6S6W; 6TE5; 6TGW; 6TRY; 7A6Q; 7QK7; 7QK8; 7QK9
• EC Number: 1.2.1.36
• Pfam ID: PF00171
• Sequence:
  MATANGAVENGQPDRKPPALPRPIRNLEVKFTKIFINNEWHESKSGKKFATCNPSTREQI
  CEVEEGDKPDVDKAVEAAQVAFQRGSPWRRLDALSRGRLLHQLADLVERDRATLAALETM
  DTGKPFLHAFFIDLEGCIRTLRYFAGWADKIQGKTIPTDDNVVCFTRHEPIGVCGAITPW
  NFPLLMLVWKLAPALCCGNTMVLKPAEQTPLTALYLGSLIKEAGFPPGVVNIVPGFGPTV
  GAAISSHPQINKIAFTGSTEVGKLVKEAASRSNLKRVTLELGGKNPCIVCADADLDLAVE
  CAHQGVFFNQGQCCTAASRVFVEEQVYSEFVRRSVEYAKKRPVGDPFDVKTEQGPQIDQK
  QFDKILELIESGKKEGAKLECGGSAMEDKGLFIKPTVFSEVTDNMRIAKEEIFGPVQPIL
  KFKSIEEVIKRANSTDYGLTAAVFTKNLDKALKLASALESGTVWINCYNALYAQAPFGGF
  KMSGNGRELGEYALAEYTEVKTVTIKLGDKNP
• Function: Catalyzes the NAD-dependent oxidation of aldehyde substrates, such as all-trans-retinal and all-trans-13,14-dihydroretinal, to their corresponding carboxylic acids, all-trans-retinoate and all-trans-13,14-dihydroretinoate, respectively. High specificity for all-trans-retinal as substrate, can also accept acetaldehyde as substrate in vitro but with lower affinity. Required for the biosynthesis of normal levels of retinoate in the embryonic ocular and nasal regions; a critical lipid in the embryonic development of the eye and the nasal region.
• Tissue Specificity: Expressed at low levels in many tissues and at higher levels in salivary gland, stomach, and kidney.
• KEGG Pathway:
  Retinol metabolism (hsa00830)
  Metabolic pathways (hsa01100)
• Reactome Pathway: RA biosynthesis pathway (R-HSA-5365859)
• BioCyc Pathway: MetaCyc:HS00013-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Definitive	Altered Expression	[1]
HER2/NEU overexpressing breast cancer	DISYKID5	Definitive	Altered Expression	[2]
Non-small-cell lung cancer	DIS5Y6R9	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[4]
Brain cancer	DISBKFB7	Strong	Biomarker	[5]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[6]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[7]
Coloboma	DISP39N5	Strong	Genetic Variation	[8]
Colon cancer	DISVC52G	Strong	Biomarker	[9]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[9]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[11]
Congenital contractural arachnodactyly	DISOM1K7	Strong	Biomarker	[12]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[10]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[13]
Gallbladder cancer	DISXJUAF	Strong	Biomarker	[14]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[5]
Glioma	DIS5RPEH	Strong	Biomarker	[15]
Isolated microphthalmia 8	DISTH264	Strong	Autosomal recessive	[16]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[17]
Lung cancer	DISCM4YA	Strong	Biomarker	[18]
Lung carcinoma	DISTR26C	Strong	Biomarker	[18]
Malignant glioma	DISFXKOV	Strong	Biomarker	[19]
Melanoma	DIS1RRCY	Strong	Altered Expression	[20]
Metastatic melanoma	DISSL43L	Strong	Altered Expression	[20]
Neoplasm	DISZKGEW	Strong	Posttranslational Modification	[15]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[21]
Pervasive developmental disorder	DIS51975	Strong	Genetic Variation	[22]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Altered Expression	[23]
Testicular germ cell tumor	DIS5RN24	Strong	Altered Expression	[24]
Breast neoplasm	DISNGJLM	moderate	Biomarker	[25]
Meningioma	DISPT4TG	moderate	Genetic Variation	[26]
Prostate cancer	DISF190Y	moderate	Altered Expression	[27]
Prostate carcinoma	DISMJPLE	moderate	Altered Expression	[27]
Isolated anophthalmia-microphthalmia syndrome	DISA55ZA	Supportive	Autosomal dominant	[16]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[5]
Gastric cancer	DISXGOUK	Limited	Biomarker	[28]
Gastric neoplasm	DISOKN4Y	Limited	Biomarker	[28]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Limited	Biomarker	[28]
Malignant pleural mesothelioma	DIST2R60	Limited	Altered Expression	[29]
Meckel syndrome, type 1	DIS4YWZU	Limited	Biomarker	[30]
Microphthalmia	DISGEBES	Limited	Genetic Variation	[31]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[32]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[33]
Triple negative breast cancer	DISAMG6N	Limited	Biomarker	[25]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Retinaldehyde dehydrogenase 3 (ALDH1A3) affects the response to substance of Temozolomide.	[67]
DTI-015	DMXZRW0	Approved	Retinaldehyde dehydrogenase 3 (ALDH1A3) affects the response to substance of DTI-015.	[67]
Disulfiram	DMCL2OK	Phase 2 Trial	Retinaldehyde dehydrogenase 3 (ALDH1A3) increases the Dyspnoeas ADR of Disulfiram.	[68]
NAPQI	DM8F5LR	Investigative	Retinaldehyde dehydrogenase 3 (ALDH1A3) affects the response to substance of NAPQI.	[69]

This DOT Affected the Biotransformations of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
All-trans-retinal	DM6CEVB	Investigative	Retinaldehyde dehydrogenase 3 (ALDH1A3) increases the oxidation of All-trans-retinal.	[51]

41 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 Retinaldehyde dehydrogenase 3 (ALDH1A3).	[34]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[35]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[36]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[37]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[38]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[39]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[40]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[39]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[28]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[42]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[43]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[44]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[40]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[45]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[46]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[47]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[36]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[48]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[36]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[36]
Enzalutamide	DMGL19D	Approved	Enzalutamide decreases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[49]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[36]
Omeprazole	DM471KJ	Approved	Omeprazole increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[50]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[51]
Isoflavone	DM7U58J	Phase 4	Isoflavone affects the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[52]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[40]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[53]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[54]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[55]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[57]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[37]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[58]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[59]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[60]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[61]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[62]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[63]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[51]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[64]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[65]
PP-242	DM2348V	Investigative	PP-242 increases the expression of Retinaldehyde dehydrogenase 3 (ALDH1A3).	[66]

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 Retinaldehyde dehydrogenase 3 (ALDH1A3).	[56]

References

• [1] Essential role of aldehyde dehydrogenase 1A3 for the maintenance of non-small cell lung cancer stem cells is associated with the STAT3 pathway.Clin Cancer Res. 2014 Aug 1;20(15):4154-66. doi: 10.1158/1078-0432.CCR-13-3292. Epub 2014 Jun 6.
• [2] Identification of new cancer stem cell markers and signaling pathways in HER?positive breast cancer by transcriptome sequencing.Int J Oncol. 2019 Nov;55(5):1003-1018. doi: 10.3892/ijo.2019.4876. Epub 2019 Sep 12.
• [3] Inhibitors of aldehyde dehydrogenases of the 1A subfamily as putative anticancer agents: Kinetic characterization and effect on human cancer cells.Chem Biol Interact. 2019 Jun 1;306:123-130. doi: 10.1016/j.cbi.2019.04.004. Epub 2019 Apr 5.
• [4] Whole-Exome Sequencing in a South American Cohort Links ALDH1A3, FOXN1 and Retinoic Acid Regulation Pathways to Autism Spectrum Disorders.PLoS One. 2015 Sep 9;10(9):e0135927. doi: 10.1371/journal.pone.0135927. eCollection 2015.
• [5] Deubiquitinating ALDH1A3 key to maintaining the culprit of aggressive brain cancer.J Clin Invest. 2019 Apr 8;129(5):1833-1835. doi: 10.1172/JCI128742. eCollection 2019 Apr 8.
• [6] Inhibition of breast cancer growth via miR-7 suppressing ALDH1A3 activity concomitant with decreasing breast cancer stem cell subpopulation.J Cell Physiol. 2020 Feb;235(2):1405-1416. doi: 10.1002/jcp.29059. Epub 2019 Jul 25.
• [7] ALDH1A3, the Major Aldehyde Dehydrogenase Isoform in Human Cholangiocarcinoma Cells, Affects Prognosis and Gemcitabine Resistance in Cholangiocarcinoma Patients.Clin Cancer Res. 2016 Aug 15;22(16):4225-35. doi: 10.1158/1078-0432.CCR-15-1800. Epub 2016 Apr 13.
• [8] The genetic architecture of microphthalmia, anophthalmia and coloboma. Eur J Med Genet. 2014 Aug;57(8):369-80. doi: 10.1016/j.ejmg.2014.05.002. Epub 2014 May 22.
• [9] ALDH1A3 affects colon cancer in vitro proliferation and invasion depending on CXCR4 status.Br J Cancer. 2018 Jan;118(2):224-232. doi: 10.1038/bjc.2017.363. Epub 2017 Dec 12.
• [10] Oncogenic targets Mmp7, S100a9, Nppb and Aldh1a3 from transcriptome profiling of FAP and Pirc adenomas are downregulated in response to tumor suppression by Clotam.Int J Cancer. 2017 Jan 15;140(2):460-468. doi: 10.1002/ijc.30458. Epub 2016 Oct 18.
• [11] ALDH1A3 upregulation and spontaneous metastasis formation is associated with acquired chemoresistance in colorectal cancer cells.BMC Cancer. 2018 Aug 24;18(1):848. doi: 10.1186/s12885-018-4758-y.
• [12] Aberrant methylation of HTATIP2 and UCHL1 as a predictive biomarker for cholangiocarcinoma.Mol Med Rep. 2018 Mar;17(3):4145-4153. doi: 10.3892/mmr.2017.8319. Epub 2017 Dec 19.
• [13] Altered hepatic genes related to retinol metabolism and plasma retinol in patients with non-alcoholic fatty liver disease.PLoS One. 2018 Oct 31;13(10):e0205747. doi: 10.1371/journal.pone.0205747. eCollection 2018.
• [14] Positive ALDH1A3 and negative GPX3 expressions are biomarkers for poor prognosis of gallbladder cancer.Dis Markers. 2013;35(3):163-72. doi: 10.1155/2013/187043. Epub 2013 Aug 25.
• [15] High expression of ALDH1A3 might independently influence poor progression-free and overall survival in patients with glioma via maintaining glucose uptake and lactate production.Cell Biol Int. 2020 Feb;44(2):569-582. doi: 10.1002/cbin.11257. Epub 2019 Nov 7.
• [16] ALDH1A3 mutations cause recessive anophthalmia and microphthalmia. Am J Hum Genet. 2013 Feb 7;92(2):265-70. doi: 10.1016/j.ajhg.2012.12.003. Epub 2013 Jan 9.
• [17] Targeting USP22 Suppresses Tumorigenicity and Enhances Cisplatin Sensitivity Through ALDH1A3 Downregulation in Cancer-Initiating Cells from Lung Adenocarcinoma.Mol Cancer Res. 2018 Jul;16(7):1161-1171. doi: 10.1158/1541-7786.MCR-18-0042. Epub 2018 May 2.
• [18] Stem cell-like ALDH(bright) cellular states in EGFR-mutant non-small cell lung cancer: a novel mechanism of acquired resistance to erlotinib targetable with the natural polyphenol silibinin.Cell Cycle. 2013 Nov 1;12(21):3390-404. doi: 10.4161/cc.26417. Epub 2013 Sep 17.
• [19] ALDH1A3 induces mesenchymal differentiation and serves as a predictor for survival in glioblastoma.Cell Death Dis. 2018 Dec 11;9(12):1190. doi: 10.1038/s41419-018-1232-3.
• [20] Clinical implications of ALDH1A1 and ALDH1A3 mRNA expression in melanoma subtypes.Chem Biol Interact. 2019 Dec 1;314:108822. doi: 10.1016/j.cbi.2019.108822. Epub 2019 Sep 30.
• [21] An integrated transcriptome and epigenome analysis identifies a novel candidate gene for pancreatic cancer.BMC Med Genomics. 2013 Sep 22;6:33. doi: 10.1186/1755-8794-6-33.
• [22] A homozygous mutation in a consanguineous family consolidates the role of ALDH1A3 in autosomal recessive microphthalmia.Clin Genet. 2014 Sep;86(3):276-81. doi: 10.1111/cge.12277. Epub 2013 Oct 25.
• [23] The molecular phenotype of polycystic ovary syndrome (PCOS) theca cells and new candidate PCOS genes defined by microarray analysis.J Biol Chem. 2003 Jul 18;278(29):26380-90. doi: 10.1074/jbc.M300688200. Epub 2003 May 6.
• [24] Disulfiram Overcomes Cisplatin Resistance in Human Embryonal Carcinoma Cells.Cancers (Basel). 2019 Aug 22;11(9):1224. doi: 10.3390/cancers11091224.
• [25] ALDH1A3-regulated long non-coding RNA NRAD1 is a potential novel target for triple-negative breast tumors and cancer stem cells.Cell Death Differ. 2020 Jan;27(1):363-378. doi: 10.1038/s41418-019-0362-1. Epub 2019 Jun 13.
• [26] Overexpression of aryl hydrocarbon receptor (AHR) signalling pathway in human meningioma.J Neurooncol. 2018 Apr;137(2):241-248. doi: 10.1007/s11060-017-2730-3. Epub 2018 Jan 4.
• [27] ALDH1A3 correlates with luminal phenotype in prostate cancer.Tumour Biol. 2017 Apr;39(4):1010428317703652. doi: 10.1177/1010428317703652.
• [28] Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006 Jan;97(1):64-71.
• [29] A STAT3-NFkB/DDIT3/CEBP axis modulates ALDH1A3 expression in chemoresistant cell subpopulations.Oncotarget. 2015 May 20;6(14):12637-53. doi: 10.18632/oncotarget.3703.
• [30] Mesenchymal glioma stem cells are maintained by activated glycolytic metabolism involving aldehyde dehydrogenase 1A3.Proc Natl Acad Sci U S A. 2013 May 21;110(21):8644-9. doi: 10.1073/pnas.1221478110. Epub 2013 May 6.
• [31] Novel mutations in ALDH1A3 associated with autosomal recessive anophthalmia/microphthalmia, and review of the literature.BMC Med Genet. 2018 Sep 10;19(1):160. doi: 10.1186/s12881-018-0678-6.
• [32] Aldehyde dehydrogenase activity plays a Key role in the aggressive phenotype of neuroblastoma.BMC Cancer. 2016 Oct 10;16(1):781. doi: 10.1186/s12885-016-2820-1.
• [33] Aldehyde dehydrogenase 1A3 influences breast cancer progression via differential retinoic acid signaling.Mol Oncol. 2015 Jan;9(1):17-31. doi: 10.1016/j.molonc.2014.07.010. Epub 2014 Jul 24.
• [34] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [35] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [36] 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.
• [37] Editor's Highlight: Transcriptome Profiling Reveals Bisphenol A Alternatives Activate Estrogen Receptor Alpha in Human Breast Cancer Cells. Toxicol Sci. 2017 Aug 1;158(2):431-443. doi: 10.1093/toxsci/kfx101.
• [38] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [39] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [40] 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.
• [41] Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006 Jan;97(1):64-71.
• [42] 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.
• [43] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [44] Dissecting progressive stages of 5-fluorouracil resistance in vitro using RNA expression profiling. Int J Cancer. 2004 Nov 1;112(2):200-12. doi: 10.1002/ijc.20401.
• [45] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [46] 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.
• [47] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [48] 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.
• [49] 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.
• [50] Evaluation of gene induction of drug-metabolizing enzymes and transporters in primary culture of human hepatocytes using high-sensitivity real-time reverse transcription PCR. Yakugaku Zasshi. 2002 May;122(5):339-61.
• [51] Androgen regulation of aldehyde dehydrogenase 1A3 (ALDH1A3) in the androgen-responsive human prostate cancer cell line LNCaP. Exp Biol Med (Maywood). 2007 Jun;232(6):762-71.
• [52] Soy isoflavones alter expression of genes associated with cancer progression, including interleukin-8, in androgen-independent PC-3 human prostate cancer cells. J Nutr. 2006 Jan;136(1):75-82.
• [53] Differential effects of resveratrol on androgen-responsive LNCaP human prostate cancer cells in vitro and in vivo. Carcinogenesis. 2008 Oct;29(10):2001-10.
• [54] Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
• [55] Using DNA microarray analyses to elucidate the effects of genistein in androgen-responsive prostate cancer cells: identification of novel targets. Mol Carcinog. 2004 Oct;41(2):108-119.
• [56] 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.
• [57] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [58] 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.
• [59] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [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] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [62] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [63] Evaluation of estrogen receptor alpha activation by glyphosate-based herbicide constituents. Food Chem Toxicol. 2017 Oct;108(Pt A):30-42.
• [64] Early gene response in lithium chloride induced apoptosis. Apoptosis. 2005 Jan;10(1):75-90. doi: 10.1007/s10495-005-6063-x.
• [65] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.
• [66] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.
• [67] 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.
• [68] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [69] Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci. 2011 Mar;120(1):33-41. doi: 10.1093/toxsci/kfq375. Epub 2010 Dec 22.
• [70] Androgen regulation of aldehyde dehydrogenase 1A3 (ALDH1A3) in the androgen-responsive human prostate cancer cell line LNCaP. Exp Biol Med (Maywood). 2007 Jun;232(6):762-71.