Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT71X1AK)

• DOT Name: Triple functional domain protein (TRIO)
• Synonyms: EC 2.7.11.1; PTPRF-interacting protein
• Gene Name: TRIO
• Related Disease:
  Syndromic intellectual disability
  Acute myelogenous leukaemia
  Adenocarcinoma
  Autism
  Autism spectrum disorder
  B-cell neoplasm
  Bladder cancer
  Cerebellar ataxia
  Cervical cancer
  Cervical carcinoma
  Colorectal carcinoma
  Glioblastoma multiforme
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Her2-receptor negative breast cancer
  Infantile epileptic-dyskinetic encephalopathy
  Intellectual disability, autosomal dominant 40
  Liver cancer
  Major depressive disorder
  Malignant peripheral nerve sheath tumor
  Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  Neurodevelopmental disorder
  Osteoarthritis
  Osteoporosis
  Pervasive developmental disorder
  Precancerous condition
  Urinary bladder cancer
  Urinary bladder neoplasm
  Uveal Melanoma
  Advanced cancer
  High blood pressure
  Intellectual developmental disorder, autosomal dominant 63, with macrocephaly
  Intellectual disability
  Liver cirrhosis
  Neoplasm
  Pinta disease
  Epilepsy
  Liposarcoma
  Metastatic prostate carcinoma
  Schizophrenia
• UniProt ID: TRIO_HUMAN
• PDB ID: 1NTY; 2NZ8; 6D8Z; 7SJ4
• EC Number: 2.7.11.1
• Pfam ID: PF13716 ; PF07679 ; PF00169 ; PF00069 ; PF00621 ; PF16609 ; PF00018 ; PF00435
• Sequence:
  MSGSSGGAAAPAASSGPAAAASAAGSGCGGGAGEGAEEAAKDLADIAAFFRSGFRKNDEM
  KAMDVLPILKEKVAYLSGGRDKRGGPILTFPARSNHDRIRQEDLRRLISYLACIPSEEVC
  KRGFTVIVDMRGSKWDSIKPLLKILQESFPCCIHVALIIKPDNFWQKQRTNFGSSKFEFE
  TNMVSLEGLTKVVDPSQLTPEFDGCLEYNHEEWIEIRVAFEDYISNATHMLSRLEELQDI
  LAKKELPQDLEGARNMIEEHSQLKKKVIKAPIEDLDLEGQKLLQRIQSSESFPKKNSGSG
  NADLQNLLPKVSTMLDRLHSTRQHLHQMWHVRKLKLDQCFQLRLFEQDAEKMFDWITHNK
  GLFLNSYTEIGTSHPHAMELQTQHNHFAMNCMNVYVNINRIMSVANRLVESGHYASQQIR
  QIASQLEQEWKAFAAALDERSTLLDMSSIFHQKAEKYMSNVDSWCKACGEVDLPSELQDL
  EDAIHHHQGIYEHITLAYSEVSQDGKSLLDKLQRPLTPGSSDSLTASANYSKAVHHVLDV
  IHEVLHHQRQLENIWQHRKVRLHQRLQLCVFQQDVQQVLDWIENHGEAFLSKHTGVGKSL
  HRARALQKRHEDFEEVAQNTYTNADKLLEAAEQLAQTGECDPEEIYQAAHQLEDRIQDFV
  RRVEQRKILLDMSVSFHTHVKELWTWLEELQKELLDDVYAESVEAVQDLIKRFGQQQQTT
  LQVTVNVIKEGEDLIQQLRDSAISSNKTPHNSSINHIETVLQQLDEAQSQMEELFQERKI
  KLELFLQLRIFERDAIDIISDLESWNDELSQQMNDFDTEDLTIAEQRLQHHADKALTMNN
  LTFDVIHQGQDLLQYVNEVQASGVELLCDRDVDMATRVQDLLEFLHEKQQELDLAAEQHR
  KHLEQCVQLRHLQAEVKQVLGWIRNGESMLNAGLITASSLQEAEQLQREHEQFQHAIEKT
  HQSALQVQQKAEAMLQANHYDMDMIRDCAEKVASHWQQLMLKMEDRLKLVNASVAFYKTS
  EQVCSVLESLEQEYKREEDWCGGADKLGPNSETDHVTPMISKHLEQKEAFLKACTLARRN
  ADVFLKYLHRNSVNMPGMVTHIKAPEQQVKNILNELFQRENRVLHYWTMRKRRLDQCQQY
  VVFERSAKQALEWIHDNGEFYLSTHTSTGSSIQHTQELLKEHEEFQITAKQTKERVKLLI
  QLADGFCEKGHAHAAEIKKCVTAVDKRYRDFSLRMEKYRTSLEKALGISSDSNKSSKSLQ
  LDIIPASIPGSEVKLRDAAHELNEEKRKSARRKEFIMAELIQTEKAYVRDLRECMDTYLW
  EMTSGVEEIPPGIVNKELIIFGNMQEIYEFHNNIFLKELEKYEQLPEDVGHCFVTWADKF
  QMYVTYCKNKPDSTQLILEHAGSYFDEIQQRHGLANSISSYLIKPVQRITKYQLLLKELL
  TCCEEGKGEIKDGLEVMLSVPKRANDAMHLSMLEGFDENIESQGELILQESFQVWDPKTL
  IRKGRERHLFLFEMSLVFSKEVKDSSGRSKYLYKSKLFTSELGVTEHVEGDPCKFALWVG
  RTPTSDNKIVLKASSIENKQDWIKHIREVIQERTIHLKGALKEPIHIPKTAPATRQKGRR
  DGEDLDSQGDGSSQPDTISIASRTSQNTLDSDKLSGGCELTVVIHDFTACNSNELTIRRG
  QTVEVLERPHDKPDWCLVRTTDRSPAAEGLVPCGSLCIAHSRSSMEMEGIFNHKDSLSVS
  SNDASPPASVASLQPHMIGAQSSPGPKRPGNTLRKWLTSPVRRLSSGKADGHVKKLAHKH
  KKSREVRKSADAGSQKDSDDSAATPQDETVEERGRNEGLSSGTLSKSSSSGMQSCGEEEG
  EEGADAVPLPPPMAIQQHSLLQPDSQDDKASSRLLVRPTSSETPSAAELVSAIEELVKSK
  MALEDRPSSLLVDQGDSSSPSFNPSDNSLLSSSSPIDEMEERKSSSLKRRHYVLQELVET
  ERDYVRDLGYVVEGYMALMKEDGVPDDMKGKDKIVFGNIHQIYDWHRDFFLGELEKCLED
  PEKLGSLFVKHERRLHMYIAYCQNKPKSEHIVSEYIDTFFEDLKQRLGHRLQLTDLLIKP
  VQRIMKYQLLLKDFLKYSKKASLDTSELERAVEVMCIVPRRCNDMMNVGRLQGFDGKIVA
  QGKLLLQDTFLVTDQDAGLLPRCRERRIFLFEQIVIFSEPLDKKKGFSMPGFLFKNSIKV
  SCLCLEENVENDPCKFALTSRTGDVVETFILHSSSPSVRQTWIHEINQILENQRNFLNAL
  TSPIEYQRNHSGGGGGGGSGGSGGGGGSGGGGAPSGGSGHSGGPSSCGGAPSTSRSRPSR
  IPQPVRHHPPVLVSSAASSQAEADKMSGTSTPGPSLPPPGAAPEAGPSAPSRRPPGADAE
  GSEREAEPIPKMKVLESPRKGAANASGSSPDAPAKDARASLGTLPLGKPRAGAASPLNSP
  LSSAVPSLGKEPFPPSSPLQKGGSFWSSIPASPASRPGSFTFPGDSDSLQRQTPRHAAPG
  KDTDRMSTCSSASEQSVQSTQSNGSESSSSSNISTMLVTHDYTAVKEDEINVYQGEVVQI
  LASNQQNMFLVFRAATDQCPAAEGWIPGFVLGHTSAVIVENPDGTLKKSTSWHTALRLRK
  KSEKKDKDGKREGKLENGYRKSREGLSNKVSVKLLNPNYIYDVPPEFVIPLSEVTCETGE
  TVVLRCRVCGRPKASITWKGPEHNTLNNDGHYSISYSDLGEATLKIVGVTTEDDGIYTCI
  AVNDMGSASSSASLRVLGPGMDGIMVTWKDNFDSFYSEVAELGRGRFSVVKKCDQKGTKR
  AVATKFVNKKLMKRDQVTHELGILQSLQHPLLVGLLDTFETPTSYILVLEMADQGRLLDC
  VVRWGSLTEGKIRAHLGEVLEAVRYLHNCRIAHLDLKPENILVDESLAKPTIKLADFGDA
  VQLNTTYYIHQLLGNPEFAAPEIILGNPVSLTSDTWSVGVLTYVLLSGVSPFLDDSVEET
  CLNICRLDFSFPDDYFKGVSQKAKEFVCFLLQEDPAKRPSAALALQEQWLQAGNGRSTGV
  LDTSRLTSFIERRKHQNDVRPIRSIKNFLQSRLLPRV
• Function: Guanine nucleotide exchange factor (GEF) for RHOA and RAC1 GTPases. Involved in coordinating actin remodeling, which is necessary for cell migration and growth. Plays a key role in the regulation of neurite outgrowth and lamellipodia formation. In developing hippocampal neurons, limits dendrite formation, without affecting the establishment of axon polarity. Once dendrites are formed, involved in the control of synaptic function by regulating the endocytosis of AMPA-selective glutamate receptors (AMPARs) at CA1 excitatory synapses. May act as a regulator of adipogenesis.
• Tissue Specificity: Widely expressed, with highest levels in heart, skeletal muscle, and brain.
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  G alpha (12/13) signalling events (R-HSA-416482)
  DCC mediated attractive signaling (R-HSA-418885)
  RHOA GTPase cycle (R-HSA-8980692)
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC2 GTPase cycle (R-HSA-9013404)
  RHOG GTPase cycle (R-HSA-9013408)
  RHOJ GTPase cycle (R-HSA-9013409)
  RAC3 GTPase cycle (R-HSA-9013423)
  NRAGE signals death through JNK (R-HSA-193648)

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Syndromic intellectual disability	DISH7SDF	Definitive	Autosomal dominant	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[3]
Autism	DISV4V1Z	Strong	Genetic Variation	[4]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[5]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[6]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[7]
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[8]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[9]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[10]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[11]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[6]
Her2-receptor negative breast cancer	DISS605N	Strong	Biomarker	[13]
Infantile epileptic-dyskinetic encephalopathy	DISD2ZNC	Strong	Genetic Variation	[14]
Intellectual disability, autosomal dominant 40	DISAI0IH	Strong	Autosomal dominant	[5]
Liver cancer	DISDE4BI	Strong	Biomarker	[15]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[16]
Malignant peripheral nerve sheath tumor	DIS0JTN6	Strong	Altered Expression	[17]
Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome	DISK8N8S	Strong	Autosomal dominant	[18]
Neurodevelopmental disorder	DIS372XH	Strong	Biomarker	[4]
Osteoarthritis	DIS05URM	Strong	Biomarker	[19]
Osteoporosis	DISF2JE0	Strong	Genetic Variation	[20]
Pervasive developmental disorder	DIS51975	Strong	Biomarker	[5]
Precancerous condition	DISV06FL	Strong	Biomarker	[15]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[7]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[7]
Uveal Melanoma	DISA7ZGL	Strong	Biomarker	[21]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[22]
High blood pressure	DISY2OHH	moderate	Biomarker	[23]
Intellectual developmental disorder, autosomal dominant 63, with macrocephaly	DIS3DB5D	Moderate	Autosomal dominant	[18]
Intellectual disability	DISMBNXP	moderate	Genetic Variation	[24]
Liver cirrhosis	DIS4G1GX	moderate	Biomarker	[25]
Neoplasm	DISZKGEW	moderate	Altered Expression	[26]
Pinta disease	DISZ0SD8	moderate	Biomarker	[27]
Epilepsy	DISBB28L	Limited	Genetic Variation	[4]
Liposarcoma	DIS8IZVM	Limited	Biomarker	[28]
Metastatic prostate carcinoma	DISVBEZ9	Limited	Biomarker	[29]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorothiazide	DMLHESP	Approved	Triple functional domain protein (TRIO) increases the Peripheral sensory neuropathy ADR of Chlorothiazide.	[48]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Triple functional domain protein (TRIO).	[30]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Triple functional domain protein (TRIO).	[43]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Triple functional domain protein (TRIO).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Triple functional domain protein (TRIO).	[45]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Triple functional domain protein (TRIO).	[44]

15 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 Triple functional domain protein (TRIO).	[31]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Triple functional domain protein (TRIO).	[32]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Triple functional domain protein (TRIO).	[33]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Triple functional domain protein (TRIO).	[34]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Triple functional domain protein (TRIO).	[35]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Triple functional domain protein (TRIO).	[36]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Triple functional domain protein (TRIO).	[37]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Triple functional domain protein (TRIO).	[38]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Triple functional domain protein (TRIO).	[39]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Triple functional domain protein (TRIO).	[40]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Triple functional domain protein (TRIO).	[41]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Triple functional domain protein (TRIO).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Triple functional domain protein (TRIO).	[42]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Triple functional domain protein (TRIO).	[46]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Triple functional domain protein (TRIO).	[47]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Epigenetic-based treatments emphasize the biologic differences of core-binding factor acute myeloid leukemias.Leuk Res. 2008 Jun;32(6):944-53. doi: 10.1016/j.leukres.2007.11.038. Epub 2008 Feb 21.
• [3] HER2 Status in Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma for Entry to the TRIO-013/LOGiC Trial of Lapatinib.Mol Cancer Ther. 2017 Jan;16(1):228-238. doi: 10.1158/1535-7163.MCT-15-0887. Epub 2016 Nov 3.
• [4] Trio Haploinsufficiency Causes Neurodevelopmental Disease-Associated Deficits.Cell Rep. 2019 Mar 5;26(10):2805-2817.e9. doi: 10.1016/j.celrep.2019.02.022.
• [5] Incorporating Functional Information in Tests of Excess De Novo Mutational Load. Am J Hum Genet. 2015 Aug 6;97(2):272-83. doi: 10.1016/j.ajhg.2015.06.013. Epub 2015 Jul 30.
• [6] Upregulated TRIO expression correlates with a malignant phenotype in human hepatocellular carcinoma.Tumour Biol. 2015 Sep;36(9):6901-8. doi: 10.1007/s13277-015-3377-3. Epub 2015 Apr 8.
• [7] TRIO amplification and abundant mRNA expression is associated with invasive tumor growth and rapid tumor cell proliferation in urinary bladder cancer.Am J Pathol. 2004 Jul;165(1):63-9. doi: 10.1016/S0002-9440(10)63275-0.
• [8] TRIO gene segregation in a family with cerebellar ataxia.Neurol Neurochir Pol. 2018 Nov-Dec;52(6):743-749. doi: 10.1016/j.pjnns.2018.09.006. Epub 2018 Sep 22.
• [9] Knockdown of Trio by CRISPR/Cas9 suppresses migration and invasion of cervical cancer cells.Oncol Rep. 2018 Feb;39(2):795-801. doi: 10.3892/or.2017.6117. Epub 2017 Nov 28.
• [10] Promotion of colorectal cancer invasion and metastasis through activation of NOTCH-DAB1-ABL-RHOGEF protein TRIO.Cancer Discov. 2015 Feb;5(2):198-211. doi: 10.1158/2159-8290.CD-14-0595. Epub 2014 Nov 28.
• [11] The guanine nucleotide exchange factors trio, Ect2, and Vav3 mediate the invasive behavior of glioblastoma.Am J Pathol. 2008 Dec;173(6):1828-38. doi: 10.2353/ajpath.2008.080043. Epub 2008 Nov 13.
• [12] Potent viral suppression and improvements in alpha-fetoprotein and measures of fibrosis in Japanese patients receiving a daclatasvir/asunaprevir/beclabuvir fixed-dose combination for the treatment of HCV genotype-1 infection.J Gastroenterol. 2018 Sep;53(9):1089-1097. doi: 10.1007/s00535-018-1445-3. Epub 2018 Mar 2.
• [13] Beta blockers and improved progression-free survival in patients with advanced HER2 negative breast cancer: a retrospective analysis of the ROSE/TRIO-012 study.Ann Oncol. 2017 Aug 1;28(8):1836-1841. doi: 10.1093/annonc/mdx264.
• [14] A de novo SCN8A heterozygous mutation in a child with epileptic encephalopathy: a case report.BMC Pediatr. 2019 Nov 1;19(1):400. doi: 10.1186/s12887-019-1796-9.
• [15] Multiple genes exhibit phenobarbital-induced constitutive active/androstane receptor-mediated DNA methylation changes during liver tumorigenesis and in liver tumors.Toxicol Sci. 2009 Apr;108(2):273-89. doi: 10.1093/toxsci/kfp031. Epub 2009 Feb 20.
• [16] The PHF21B gene is associated with major depression and modulates the stress response.Mol Psychiatry. 2017 Jul;22(7):1015-1025. doi: 10.1038/mp.2016.174. Epub 2016 Oct 25.
• [17] Frequent amplifications and abundant expression of TRIO, NKD2, and IRX2 in soft tissue sarcomas.Genes Chromosomes Cancer. 2006 Sep;45(9):829-38. doi: 10.1002/gcc.20343.
• [18] 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.
• [19] SOX trio decrease in the articular cartilage with the advancement of osteoarthritis.Connect Tissue Res. 2011;52(6):496-502. doi: 10.3109/03008207.2011.585409. Epub 2011 Jul 5.
• [20] The effect of bisphosphosphonates on bone turnover and bone balance in postmenopausal women with osteoporosis: The T-score bone marker approach in the TRIO study.Bone. 2020 Feb;131:115158. doi: 10.1016/j.bone.2019.115158. Epub 2019 Nov 15.
• [21] A Platform of Synthetic Lethal Gene Interaction Networks Reveals that the GNAQ Uveal Melanoma Oncogene Controls the Hippo Pathway through FAK.Cancer Cell. 2019 Mar 18;35(3):457-472.e5. doi: 10.1016/j.ccell.2019.01.009. Epub 2019 Feb 14.
• [22] Managing challenging interactions with family caregivers in the cancer setting: Guidelines for clinicians (TRIO Guidelines-2).Patient Educ Couns. 2018 Jun;101(6):983-994. doi: 10.1016/j.pec.2018.01.020. Epub 2018 Feb 2.
• [23] A multinational clinical approach to assessing the effectiveness of catheter-based ultrasound renal denervation: The RADIANCE-HTN and REQUIRE clinical study designs.Am Heart J. 2018 Jan;195:115-129. doi: 10.1016/j.ahj.2017.09.006. Epub 2017 Sep 12.
• [24] Evolution of the Rho guanine nucleotide exchange factors Kalirin and Trio and their gene expression in Xenopus development.Gene Expr Patterns. 2019 Jun;32:18-27. doi: 10.1016/j.gep.2019.02.004. Epub 2019 Mar 4.
• [25] Pharmacokinetic and pharmacodynamic evaluation of daclatasvir, asunaprevir plus beclabuvir as a fixed-dose co-formulation for the treatment of hepatitis C.Expert Opin Drug Metab Toxicol. 2018 Jun;14(6):649-657. doi: 10.1080/17425255.2018.1483336. Epub 2018 Jun 10.
• [26] Integrin-10 Dependency Identifies RAC and RICTOR as Therapeutic Targets in High-Grade Myxofibrosarcoma.Cancer Discov. 2016 Oct;6(10):1148-1165. doi: 10.1158/2159-8290.CD-15-1481. Epub 2016 Aug 30.
• [27] Copy Number Variation and Expression Analysis Reveals a Nonorthologous Pinta Gene Family Member Involved in Butterfly Vision.Genome Biol Evol. 2017 Dec 1;9(12):3398-3412. doi: 10.1093/gbe/evx230.
• [28] Spindle cell liposarcoma with a TRIO-TERT fusion transcript.Virchows Arch. 2019 Sep;475(3):391-394. doi: 10.1007/s00428-019-02545-5. Epub 2019 Feb 22.
• [29] HSP27, ALDH6A1 and Prohibitin Act as a Trio-biomarker to Predict Survival in Late Metastatic Prostate Cancer.Anticancer Res. 2018 Nov;38(11):6551-6560. doi: 10.21873/anticanres.13021.
• [30] 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.
• [31] 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.
• [32] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [33] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [34] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [35] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [36] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [37] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [38] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [39] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [40] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [41] 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.
• [42] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [43] 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.
• [44] 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.
• [45] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [46] 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.
• [47] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.
• [48] Genome-wide association study identifies ephrin type A receptors implicated in paclitaxel induced peripheral sensory neuropathy. J Med Genet. 2013 Sep;50(9):599-605. doi: 10.1136/jmedgenet-2012-101466. Epub 2013 Jun 17.