Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLL92LQ)

• DOT Name: RE1-silencing transcription factor (REST)
• Synonyms: Neural-restrictive silencer factor; X2 box repressor
• Gene Name: REST
• Related Disease:
  Anxiety
  Anxiety disorder
  Autism spectrum disorder
  Bone osteosarcoma
  Brain neoplasm
  Breast cancer
  Breast neoplasm
  Cerebral infarction
  Depression
  Epilepsy
  Epithelial ovarian cancer
  Fibromatosis, gingival, 1
  Fibromatosis, gingival, 5
  Huntington disease
  Lung cancer
  Lung carcinoma
  Major depressive disorder
  Mental disorder
  Neuralgia
  Neuroblastoma
  Ovarian cancer
  Ovarian neoplasm
  Parkinson disease
  Prostate cancer
  Prostate carcinoma
  Sarcoma
  Stroke
  Triple negative breast cancer
  Wilms tumor
  Wilms tumor 6
  X-linked intellectual disability
  Cholangiocarcinoma
  Coronary heart disease
  Hepatocellular carcinoma
  Melanoma
  Nervous system disease
  Pancreatic cancer
  Squamous cell carcinoma
  Hereditary gingival fibromatosis
  Glioblastoma multiforme
  Adult glioblastoma
  Amyotrophic lateral sclerosis
  Autosomal dominant nonsyndromic hearing loss 27
  Breast carcinoma
  Cognitive impairment
  Colorectal carcinoma
  Schizophrenia
  Small-cell lung cancer
  Type-1/2 diabetes
• UniProt ID: REST_HUMAN
• PDB ID: 2CZY; 6DU2; 6DU3
• Pfam ID: PF00096
• Sequence:
  MATQVMGQSSGGGGLFTSSGNIGMALPNDMYDLHDLSKAELAAPQLIMLANVALTGEVNG
  SCCDYLVGEERQMAELMPVGDNNFSDSEEGEGLEESADIKGEPHGLENMELRSLELSVVE
  PQPVFEASGAPDIYSSNKDLPPETPGAEDKGKSSKTKPFRCKPCQYEAESEEQFVHHIRV
  HSAKKFFVEESAEKQAKARESGSSTAEEGDFSKGPIRCDRCGYNTNRYDHYTAHLKHHTR
  AGDNERVYKCIICTYTTVSEYHWRKHLRNHFPRKVYTCGKCNYFSDRKNNYVQHVRTHTG
  ERPYKCELCPYSSSQKTHLTRHMRTHSGEKPFKCDQCSYVASNQHEVTRHARQVHNGPKP
  LNCPHCDYKTADRSNFKKHVELHVNPRQFNCPVCDYAASKKCNLQYHFKSKHPTCPNKTM
  DVSKVKLKKTKKREADLPDNITNEKTEIEQTKIKGDVAGKKNEKSVKAEKRDVSKEKKPS
  NNVSVIQVTTRTRKSVTEVKEMDVHTGSNSEKFSKTKKSKRKLEVDSHSLHGPVNDEESS
  TKKKKKVESKSKNNSQEVPKGDSKVEENKKQNTCMKKSTKKKTLKNKSSKKSSKPPQKEP
  VEKGSAQMDPPQMGPAPTEAVQKGPVQVEPPPPMEHAQMEGAQIRPAPDEPVQMEVVQEG
  PAQKELLPPVEPAQMVGAQIVLAHMELPPPMETAQTEVAQMGPAPMEPAQMEVAQVESAP
  MQVVQKEPVQMELSPPMEVVQKEPVQIELSPPMEVVQKEPVKIELSPPIEVVQKEPVQME
  LSPPMGVVQKEPAQREPPPPREPPLHMEPISKKPPLRKDKKEKSNMQSERARKEQVLIEV
  GLVPVKDSWLLKESVSTEDLSPPSPPLPKENLREEASGDQKLLNTGEGNKEAPLQKVGAE
  EADESLPGLAANINESTHISSSGQNLNTPEGETLNGKHQTDSIVCEMKMDTDQNTRENLT
  GINSTVEEPVSPMLPPSAVEEREAVSKTALASPPATMAANESQEIDEDEGIHSHEGSDLS
  DNMSEGSDDSGLHGARPVPQESSRKNAKEALAVKAAKGDFVCIFCDRSFRKGKDYSKHLN
  RHLVNVYYLEEAAQGQE
• Function: Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells. Restricts the expression of neuronal genes by associating with two distinct corepressors, SIN3A and RCOR1, which in turn recruit histone deacetylase to the promoters of REST-regulated genes. Mediates repression by recruiting the BHC complex at RE1/NRSE sites which acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier. Transcriptional repression by REST-CDYL via the recruitment of histone methyltransferase EHMT2 may be important in transformation suppression. Represses the expression of SRRM4 in non-neural cells to prevent the activation of neural-specific splicing events and to prevent production of REST isoform 3. Repressor activity may be inhibited by forming heterodimers with isoform 3, thereby preventing binding to NRSE or binding to corepressors and leading to derepression of target genes. Also maintains repression of neuronal genes in neural stem cells, and allows transcription and differentiation into neurons by dissociation from RE1/NRSE sites of target genes. Thereby is involved in maintaining the quiescent state of adult neural stem cells and preventing premature differentiation into mature neurons. Plays a role in the developmental switch in synaptic NMDA receptor composition during postnatal development, by repressing GRIN2B expression and thereby altering NMDA receptor properties from containing primarily GRIN2B to primarily GRIN2A subunits. Acts as a regulator of osteoblast differentiation. Key repressor of gene expression in hypoxia; represses genes in hypoxia by direct binding to an RE1/NRSE site on their promoter regions. May also function in stress resistance in the brain during aging; possibly by regulating expression of genes involved in cell death and in the stress response. Repressor of gene expression in the hippocampus after ischemia by directly binding to RE1/NRSE sites and recruiting SIN3A and RCOR1 to promoters of target genes, thereby promoting changes in chromatin modifications and ischemia-induced cell death. After ischemia, might play a role in repression of miR-132 expression in hippocampal neurons, thereby leading to neuronal cell death. Negatively regulates the expression of SRRM3 in breast cancer cell lines ; [Isoform 3]: Binds to the 3' region of the neuron-restrictive silencer element (NRSE), with lower affinity than full-length REST isoform 1. Exhibits weaker repressor activity compared to isoform 1. May negatively regulate the repressor activity of isoform 1 by binding to isoform 1, thereby preventing its binding to NRSE and leading to derepression of target genes. However, in another study, does not appear to be implicated in repressor activity of a NRSE motif-containing reporter construct nor in inhibitory activity on the isoform 1 transcriptional repressor activity. Post-transcriptional inactivation of REST by SRRM4-dependent alternative splicing into isoform 3 is required in mechanosensory hair cells in the inner ear for derepression of neuronal genes and hearing.
• Tissue Specificity: Expressed in neurons of the prefrontal cortex, in hippocampal pyramidal neurons, dentate gyrus granule neurons and cerebellar Purkinje and granule neurons (at protein level) . Expressed in dopaminergic neurons of the substantia nigra (at protein level) . Expressed in neural progenitor cells (at protein level) . In patients suffering from Alzheimer disease, frontotemporal dementia or dementia with Lewy bodies, decreased nuclear levels have been observed in neurons of the prefrontal cortex and the hippocampus, but not in neurons of the dentate gyrus and cerebellum (at protein level) . In patients with Parkinson disease or dementia with Lewy bodies, decreased nuclear levels have been observed in dopaminergic neurons and in cortical neurons and localization to Lewy bodies and pale bodies was detected (at protein level) . Expressed at higher levels in weakly invasive breast cancer cell lines and at lower levels in highly invasive breast cancer lines (at protein level) . Ubiquitous . Expressed at higher levels in the tissues of the lymphocytic compartment, including spleen, thymus, peripheral blood lymphocytes and ovary .
• KEGG Pathway:
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
  Huntington disease (hsa05016)
• Reactome Pathway:
  Regulation of PTEN gene transcription (R-HSA-8943724)
  NGF-stimulated transcription (R-HSA-9031628)
  Potential therapeutics for SARS (R-HSA-9679191)
  Regulation of NPAS4 gene transcription (R-HSA-9768777)
  HDACs deacetylate histones (R-HSA-3214815)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anxiety	DISIJDBA	Strong	Altered Expression	[1]
Anxiety disorder	DISBI2BT	Strong	Altered Expression	[1]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[2]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[3]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[6]
Cerebral infarction	DISR1WNP	Strong	Biomarker	[7]
Depression	DIS3XJ69	Strong	Altered Expression	[1]
Epilepsy	DISBB28L	Strong	Altered Expression	[1]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[8]
Fibromatosis, gingival, 1	DIS2TQ5E	Strong	Genetic Variation	[9]
Fibromatosis, gingival, 5	DIS70VXV	Strong	Autosomal dominant	[9]
Huntington disease	DISQPLA4	Strong	Biomarker	[10]
Lung cancer	DISCM4YA	Strong	Biomarker	[6]
Lung carcinoma	DISTR26C	Strong	Biomarker	[11]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[12]
Mental disorder	DIS3J5R8	Strong	Altered Expression	[13]
Neuralgia	DISWO58J	Strong	Altered Expression	[14]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[15]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[8]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[8]
Parkinson disease	DISQVHKL	Strong	Biomarker	[16]
Prostate cancer	DISF190Y	Strong	Altered Expression	[17]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[17]
Sarcoma	DISZDG3U	Strong	Altered Expression	[3]
Stroke	DISX6UHX	Strong	Biomarker	[7]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[18]
Wilms tumor	DISB6T16	Strong	Biomarker	[19]
Wilms tumor 6	DISVAF3G	Strong	Autosomal dominant	[19]
X-linked intellectual disability	DISYJBY3	Strong	Biomarker	[20]
Cholangiocarcinoma	DIS71F6X	moderate	Altered Expression	[21]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[22]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[21]
Melanoma	DIS1RRCY	moderate	Biomarker	[23]
Nervous system disease	DISJ7GGT	moderate	Posttranslational Modification	[24]
Pancreatic cancer	DISJC981	moderate	Biomarker	[25]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[26]
Hereditary gingival fibromatosis	DISN1ML3	Supportive	Autosomal dominant	[9]
Glioblastoma multiforme	DISK8246	Disputed	Altered Expression	[27]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[28]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[29]
Autosomal dominant nonsyndromic hearing loss 27	DISOWM4Y	Limited	Autosomal dominant	[30]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[5]
Cognitive impairment	DISH2ERD	Limited	Genetic Variation	[31]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[32]
Schizophrenia	DISSRV2N	Limited	Biomarker	[33]
Small-cell lung cancer	DISK3LZD	Limited	Biomarker	[5]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[34]

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 RE1-silencing transcription factor (REST).	[35]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of RE1-silencing transcription factor (REST).	[46]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of RE1-silencing transcription factor (REST).	[48]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of RE1-silencing transcription factor (REST).	[49]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of RE1-silencing transcription factor (REST).	[36]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of RE1-silencing transcription factor (REST).	[37]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of RE1-silencing transcription factor (REST).	[38]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of RE1-silencing transcription factor (REST).	[39]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of RE1-silencing transcription factor (REST).	[40]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of RE1-silencing transcription factor (REST).	[41]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of RE1-silencing transcription factor (REST).	[42]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of RE1-silencing transcription factor (REST).	[43]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of RE1-silencing transcription factor (REST).	[44]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of RE1-silencing transcription factor (REST).	[45]
SEN-196	DMLDBQ5	Phase 2	SEN-196 increases the expression of RE1-silencing transcription factor (REST).	[45]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of RE1-silencing transcription factor (REST).	[47]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of RE1-silencing transcription factor (REST).	[50]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the activity of RE1-silencing transcription factor (REST).	[51]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of RE1-silencing transcription factor (REST).	[52]

References

• [1] REST/NRSF transcription factor is overexpressed in hippocampus of patients with drug-resistant mesial temporal lobe epilepsy.Epilepsy Behav. 2019 May;94:118-123. doi: 10.1016/j.yebeh.2019.02.012. Epub 2019 Mar 21.
• [2] mS-11, a mimetic of the mSin3-binding helix in NRSF, ameliorates social interaction deficits in a prenatal valproic acid-induced autism mouse model.Pharmacol Biochem Behav. 2019 Jan;176:1-5. doi: 10.1016/j.pbb.2018.11.003. Epub 2018 Nov 9.
• [3] Neuron-restrictive silencer factor-mediated downregulation of -opioid receptor contributes to the reduced morphine analgesia in bone cancer pain.Pain. 2017 May;158(5):879-890. doi: 10.1097/j.pain.0000000000000848.
• [4] BRAF somatic mutation contributes to intrinsic epileptogenicity in pediatric brain tumors.Nat Med. 2018 Nov;24(11):1662-1668. doi: 10.1038/s41591-018-0172-x. Epub 2018 Sep 17.
• [5] Production and characterization of monoclonal antibodies against the DNA binding domain of the RE1-silencing transcription factor.J Biochem. 2019 Nov 1;166(5):393-402. doi: 10.1093/jb/mvz046.
• [6] The transcription factor REST is lost in aggressive breast cancer.PLoS Genet. 2010 Jun 10;6(6):e1000979. doi: 10.1371/journal.pgen.1000979.
• [7] Inhibition of the Epigenetic Regulator REST Ameliorates Ischemic Brain Injury.Mol Neurobiol. 2019 Apr;56(4):2542-2550. doi: 10.1007/s12035-018-1254-y. Epub 2018 Jul 23.
• [8] Knockdown of NRSF inhibits cell proliferation of ovarian cancer via activating Hippo pathway.Life Sci. 2018 Dec 15;215:73-79. doi: 10.1016/j.lfs.2018.10.070. Epub 2018 Nov 2.
• [9] REST Final-Exon-Truncating Mutations Cause Hereditary Gingival Fibromatosis. Am J Hum Genet. 2017 Jul 6;101(1):149-156. doi: 10.1016/j.ajhg.2017.06.006.
• [10] A Combinatorial Cell and Drug Delivery Strategy for Huntington's Disease Using Pharmacologically Active Microcarriers and RNAi Neuronally-Committed Mesenchymal Stromal Cells.Pharmaceutics. 2019 Oct 12;11(10):526. doi: 10.3390/pharmaceutics11100526.
• [11] SWI/SNF complex is essential for NRSF-mediated suppression of neuronal genes in human nonsmall cell lung carcinoma cell lines.Oncogene. 2006 Jan 19;25(3):470-9. doi: 10.1038/sj.onc.1209068.
• [12] Reduced default mode network functional connectivity in patients with recurrent major depressive disorder.Proc Natl Acad Sci U S A. 2019 Apr 30;116(18):9078-9083. doi: 10.1073/pnas.1900390116. Epub 2019 Apr 12.
• [13] PDYN, a gene implicated in brain/mental disorders, is targeted by REST in the adult human brain.Biochim Biophys Acta. 2014 Nov;1839(11):1226-32. doi: 10.1016/j.bbagrm.2014.09.001. Epub 2014 Sep 8.
• [14] Sertraline, chlorprothixene, and chlorpromazine characteristically interact with the REST-binding site of the corepressor mSin3, showing medulloblastoma cell growth inhibitory activities.Sci Rep. 2018 Sep 13;8(1):13763. doi: 10.1038/s41598-018-31852-1.
• [15] The REST gene signature predicts drug sensitivity in neuroblastoma cell lines and is significantly associated with neuroblastoma tumor stage.Int J Mol Sci. 2014 Jun 25;15(7):11220-33. doi: 10.3390/ijms150711220.
• [16] The deficiency of NRSF/REST enhances the pro-inflammatory function of astrocytes in a model of Parkinson's disease.Biochim Biophys Acta Mol Basis Dis. 2020 Jan 1;1866(1):165590. doi: 10.1016/j.bbadis.2019.165590. Epub 2019 Nov 7.
• [17] Transcriptional downregulation of miR-133b by REST promotes prostate cancer metastasis to bone via activating TGF- signaling.Cell Death Dis. 2018 Jul 13;9(7):779. doi: 10.1038/s41419-018-0807-3.
• [18] The oncogenic STP axis promotes triple-negative breast cancer via degradation of the REST tumor suppressor.Cell Rep. 2014 Nov 20;9(4):1318-32. doi: 10.1016/j.celrep.2014.10.011. Epub 2014 Nov 6.
• [19] Mutations in the transcriptional repressor REST predispose to Wilms tumor. Nat Genet. 2015 Dec;47(12):1471-4. doi: 10.1038/ng.3440. Epub 2015 Nov 9.
• [20] Mediator links epigenetic silencing of neuronal gene expression with x-linked mental retardation.Mol Cell. 2008 Aug 8;31(3):347-59. doi: 10.1016/j.molcel.2008.05.023.
• [21] NRSF/REST levels are decreased in cholangiocellular carcinoma but not hepatocellular carcinoma compared with normal liver tissues: A tissue microarray study.Oncol Lett. 2018 May;15(5):6592-6598. doi: 10.3892/ol.2018.8169. Epub 2018 Mar 5.
• [22] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [23] REST negatively and ISGF3 positively regulate the human STAT1 gene in melanoma.Mol Cancer Ther. 2013 Jul;12(7):1288-98. doi: 10.1158/1535-7163.MCT-12-0923. Epub 2013 Apr 18.
• [24] REST, a master transcriptional regulator in neurodegenerative disease.Curr Opin Neurobiol. 2018 Feb;48:193-200. doi: 10.1016/j.conb.2017.12.008. Epub 2018 Jan 30.
• [25] Identification of RE1-Silencing Transcription Factor as a Promoter of Metastasis in Pancreatic Cancer.Front Oncol. 2019 Apr 16;9:291. doi: 10.3389/fonc.2019.00291. eCollection 2019.
• [26] NRSF/REST regulates the mTOR signaling pathway in oral cancer cells.Oncol Rep. 2015 Mar;33(3):1459-64. doi: 10.3892/or.2014.3675. Epub 2014 Dec 18.
• [27] FAT1 modulates EMT and stemness genes expression in hypoxic glioblastoma.Int J Cancer. 2018 Feb 15;142(4):805-812. doi: 10.1002/ijc.31092. Epub 2017 Oct 17.
• [28] Similarity in targets with REST points to neural and glioblastoma related miRNAs.Nucleic Acids Res. 2014 May;42(9):5436-46. doi: 10.1093/nar/gku231. Epub 2014 Apr 11.
• [29] Non-Methylation-Linked Mechanism of REST-Induced Neuroglobin Expression Impacts Mitochondrial Phenotypes in a Mouse Model of Amyotrophic Lateral Sclerosis.Neuroscience. 2019 Aug 1;412:233-247. doi: 10.1016/j.neuroscience.2019.05.039. Epub 2019 May 31.
• [30] 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.
• [31] Chronic Metabolic Derangement-Induced Cognitive Deficits and Neurotoxicity Are Associated with REST Inactivation.Mol Neurobiol. 2019 Mar;56(3):1539-1557. doi: 10.1007/s12035-018-1175-9. Epub 2018 Jun 14.
• [32] Long Non-coding RNA ITIH4-AS1 Accelerates the Proliferation and Metastasis of Colorectal Cancer by Activating JAK/STAT3 Signaling.Mol Ther Nucleic Acids. 2019 Dec 6;18:183-193. doi: 10.1016/j.omtn.2019.08.009. Epub 2019 Aug 16.
• [33] Dysregulated Glial Differentiation in Schizophrenia May Be Relieved by Suppression of SMAD4- and REST-Dependent Signaling.Cell Rep. 2019 Jun 25;27(13):3832-3843.e6. doi: 10.1016/j.celrep.2019.05.088.
• [34] The Importance of REST for Development and Function of Beta Cells.Front Cell Dev Biol. 2017 Feb 24;5:12. doi: 10.3389/fcell.2017.00012. eCollection 2017.
• [35] 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.
• [36] Selective Recognition of H3.1K36 Dimethylation/H4K16 Acetylation Facilitates the Regulation of All-trans-retinoic Acid (ATRA)-responsive Genes by Putative Chromatin Reader ZMYND8. J Biol Chem. 2016 Feb 5;291(6):2664-81. doi: 10.1074/jbc.M115.679985. Epub 2015 Dec 11.
• [37] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [38] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [39] 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.
• [40] 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.
• [41] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [42] 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.
• [43] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [44] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [45] Resveratrol via sirtuin-1 downregulates RE1-silencing transcription factor (REST) expression preventing PCB-95-induced neuronal cell death. Toxicol Appl Pharmacol. 2015 Nov 1;288(3):387-98. doi: 10.1016/j.taap.2015.08.010. Epub 2015 Aug 22.
• [46] 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.
• [47] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [48] 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.
• [49] 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.
• [50] Bisphenol-A exposure induced neurotoxicity in glutamatergic neurons derived from human embryonic stem cells. Environ Int. 2019 Jun;127:324-332.
• [51] Neuron restrictive silencer factor NRSF/REST is a transcriptional repressor of neuropilin-1 and diminishes the ability of semaphorin 3A to inhibit keratinocyte migration. J Biol Chem. 2006 Feb 3;281(5):2721-9. doi: 10.1074/jbc.M507860200. Epub 2005 Dec 5.
• [52] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.