Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZA2AHA)

• DOT Name: Interferon-induced helicase C domain-containing protein 1 (IFIH1)
• Synonyms: EC 3.6.4.13; Clinically amyopathic dermatomyositis autoantigen 140 kDa; CADM-140 autoantigen; Helicase with 2 CARD domains; Helicard; Interferon-induced with helicase C domain protein 1; Melanoma differentiation-associated protein 5; MDA-5; Murabutide down-regulated protein; RIG-I-like receptor 2; RLR-2; RNA helicase-DEAD box protein 116
• Gene Name: IFIH1
• Related Disease:
  Aicardi-Goutieres syndrome 7
  Advanced cancer
  Aicardi-Goutieres syndrome 1
  Aicardi-Goutieres syndrome 2
  Anemia
  Asthma
  Dengue
  Dermatomyositis
  Hashimoto thyroiditis
  Hypothyroidism
  Idiopathic inflammatory myopathy
  Influenza
  Lipodystrophy
  Lupus
  Measles
  Myotonic dystrophy type 1
  Neuroblastoma
  Palmoplantar pustulosis
  Polymyositis
  Pseudo-TORCH syndrome
  Pulmonary arterial hypertension
  Respiratory failure
  Singleton-Merten syndrome 1
  Smith-Magenis syndrome
  Thrombocytopenia
  Vascular disease
  Vitiligo
  Zika virus infection
  Chronic obstructive pulmonary disease
  Craniosynostosis
  High blood pressure
  Inflammatory bowel disease
  Multiple sclerosis
  Myositis disease
  Systemic lupus erythematosus
  Aicardi-Goutieres syndrome
  Singleton-Merten dysplasia
  Addison disease
  Ankylosing spondylitis
  Crohn disease
  Psoriasis
  Sclerosing cholangitis
  Type-1/2 diabetes
  Ulcerative colitis
• UniProt ID: IFIH1_HUMAN
• PDB ID: 2RQB; 3B6E; 3GA3; 4GL2; 7DNI; 7DNJ; 7JL0; 7JL2
• EC Number: 3.6.4.13
• Pfam ID: PF16739 ; PF00271 ; PF04851 ; PF18119 ; PF11648
• Sequence:
  MSNGYSTDENFRYLISCFRARVKMYIQVEPVLDYLTFLPAEVKEQIQRTVATSGNMQAVE
  LLLSTLEKGVWHLGWTREFVEALRRTGSPLAARYMNPELTDLPSPSFENAHDEYLQLLNL
  LQPTLVDKLLVRDVLDKCMEEELLTIEDRNRIAAAENNGNESGVRELLKRIVQKENWFSA
  FLNVLRQTGNNELVQELTGSDCSESNAEIENLSQVDGPQVEEQLLSTTVQPNLEKEVWGM
  ENNSSESSFADSSVVSESDTSLAEGSVSCLDESLGHNSNMGSDSGTMGSDSDEENVAARA
  SPEPELQLRPYQMEVAQPALEGKNIIICLPTGSGKTRVAVYIAKDHLDKKKKASEPGKVI
  VLVNKVLLVEQLFRKEFQPFLKKWYRVIGLSGDTQLKISFPEVVKSCDIIISTAQILENS
  LLNLENGEDAGVQLSDFSLIIIDECHHTNKEAVYNNIMRHYLMQKLKNNRLKKENKPVIP
  LPQILGLTASPGVGGATKQAKAEEHILKLCANLDAFTIKTVKENLDQLKNQIQEPCKKFA
  IADATREDPFKEKLLEIMTRIQTYCQMSPMSDFGTQPYEQWAIQMEKKAAKEGNRKERVC
  AEHLRKYNEALQINDTIRMIDAYTHLETFYNEEKDKKFAVIEDDSDEGGDDEYCDGDEDE
  DDLKKPLKLDETDRFLMTLFFENNKMLKRLAENPEYENEKLTKLRNTIMEQYTRTEESAR
  GIIFTKTRQSAYALSQWITENEKFAEVGVKAHHLIGAGHSSEFKPMTQNEQKEVISKFRT
  GKINLLIATTVAEEGLDIKECNIVIRYGLVTNEIAMVQARGRARADESTYVLVAHSGSGV
  IEHETVNDFREKMMYKAIHCVQNMKPEEYAHKILELQMQSIMEKKMKTKRNIAKHYKNNP
  SLITFLCKNCSVLACSGEDIHVIEKMHHVNMTPEFKELYIVRENKALQKKCADYQINGEI
  ICKCGQAWGTMMVHKGLDLPCLKIRNFVVVFKNNSTKKQYKKWVELPITFPNLDYSECCL
  FSDED
• Function: Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and pro-inflammatory cytokines. Its ligands include mRNA lacking 2'-O-methylation at their 5' cap and long-dsRNA (>1 kb in length). Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1) which activates the IKK-related kinases: TBK1 and IKBKE which phosphorylate interferon regulatory factors: IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes, including interferons (IFNs); IFN-alpha and IFN-beta. Responsible for detecting the Picornaviridae family members such as encephalomyocarditis virus (EMCV), mengo encephalomyocarditis virus (ENMG), and rhinovirus. Detects coronavirus SARS-CoV-2. Can also detect other viruses such as dengue virus (DENV), west Nile virus (WNV), and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome, such as vaccinia virus. Plays an important role in amplifying innate immune signaling through recognition of RNA metabolites that are produced during virus infection by ribonuclease L (RNase L). May play an important role in enhancing natural killer cell function and may be involved in growth inhibition and apoptosis in several tumor cell lines.
• Tissue Specificity: Widely expressed, at a low level. Expression is detected at slightly highest levels in placenta, pancreas and spleen and at barely levels in detectable brain, testis and lung.
• KEGG Pathway:
  RIG-I-like receptor sig.ling pathway (hsa04622)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Influenza A (hsa05164)
  Herpes simplex virus 1 infection (hsa05168)
  Coro.virus disease - COVID-19 (hsa05171)
• Reactome Pathway:
  Ub-specific processing proteases (R-HSA-5689880)
  Ovarian tumor domain proteases (R-HSA-5689896)
  TRAF3-dependent IRF activation pathway (R-HSA-918233)
  TRAF6 mediated IRF7 activation (R-HSA-933541)
  TRAF6 mediated NF-kB activation (R-HSA-933542)
  NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 (R-HSA-933543)
  Negative regulators of DDX58/IFIH1 signaling (R-HSA-936440)
  SARS-CoV-1 activates/modulates innate immune responses (R-HSA-9692916)
  SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671)
  DDX58/IFIH1-mediated induction of interferon-alpha/beta (R-HSA-168928)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Aicardi-Goutieres syndrome 7	DIS89BRW	Definitive	Autosomal dominant	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Aicardi-Goutieres syndrome 1	DISPAXC2	Strong	Biomarker	[1]
Aicardi-Goutieres syndrome 2	DISOL1R1	Strong	Biomarker	[1]
Anemia	DISTVL0C	Strong	CausalMutation	[3]
Asthma	DISW9QNS	Strong	Genetic Variation	[4]
Dengue	DISKH221	Strong	Altered Expression	[5]
Dermatomyositis	DIS50C5O	Strong	Biomarker	[6]
Hashimoto thyroiditis	DIS77CDF	Strong	Genetic Variation	[7]
Hypothyroidism	DISR0H6D	Strong	Genetic Variation	[4]
Idiopathic inflammatory myopathy	DISGB1BZ	Strong	Biomarker	[8]
Influenza	DIS3PNU3	Strong	Biomarker	[9]
Lipodystrophy	DIS3SGVD	Strong	Biomarker	[10]
Lupus	DISOKJWA	Strong	Biomarker	[11]
Measles	DISXSUID	Strong	Altered Expression	[12]
Myotonic dystrophy type 1	DISJC0OX	Strong	Biomarker	[13]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[14]
Palmoplantar pustulosis	DISCNSWD	Strong	Biomarker	[15]
Polymyositis	DIS5DHFP	Strong	Biomarker	[16]
Pseudo-TORCH syndrome	DISM9N8Y	Strong	Biomarker	[1]
Pulmonary arterial hypertension	DISP8ZX5	Strong	CausalMutation	[3]
Respiratory failure	DISVMYJO	Strong	Biomarker	[17]
Singleton-Merten syndrome 1	DISXY2LC	Strong	Autosomal dominant	[18]
Smith-Magenis syndrome	DISG4G6X	Strong	Biomarker	[11]
Thrombocytopenia	DISU61YW	Strong	CausalMutation	[3]
Vascular disease	DISVS67S	Strong	Biomarker	[19]
Vitiligo	DISR05SL	Strong	Biomarker	[20]
Zika virus infection	DISQUCTY	Strong	Biomarker	[21]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Altered Expression	[22]
Craniosynostosis	DIS6J405	moderate	Biomarker	[23]
High blood pressure	DISY2OHH	moderate	Altered Expression	[24]
Inflammatory bowel disease	DISGN23E	moderate	Genetic Variation	[25]
Multiple sclerosis	DISB2WZI	moderate	Genetic Variation	[26]
Myositis disease	DISCIXF0	moderate	Biomarker	[2]
Systemic lupus erythematosus	DISI1SZ7	moderate	Genetic Variation	[27]
Aicardi-Goutieres syndrome	DIS1NH4X	Supportive	Autosomal dominant	[1]
Singleton-Merten dysplasia	DISYNAVB	Supportive	Autosomal dominant	[18]
Addison disease	DIS7HNOH	Limited	Genetic Variation	[28]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[29]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[29]
Psoriasis	DIS59VMN	Limited	Biomarker	[30]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[29]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[13]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[29]

23 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 Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[31]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[32]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[34]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[35]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[36]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[37]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[38]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[39]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[40]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[41]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[40]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[40]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[40]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[40]
Hydroxychloroquine	DMSIVND	Approved	Hydroxychloroquine increases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[42]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[43]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[45]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[46]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[47]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[48]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[49]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[50]

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 Interferon-induced helicase C domain-containing protein 1 (IFIH1).	[44]

References

• [1] Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling. Nat Genet. 2014 May;46(5):503-509. doi: 10.1038/ng.2933. Epub 2014 Mar 30.
• [2] Autoantibodies in idiopathic inflammatory myopathies: Clinical associations and laboratory evaluation by mono- and multispecific immunoassays.Autoimmun Rev. 2019 Mar;18(3):293-305. doi: 10.1016/j.autrev.2018.10.004. Epub 2019 Jan 11.
• [3] An extremely severe case of Aicardi-Goutires syndrome 7 with a novel variant in IFIH1.Eur J Med Genet. 2020 Feb;63(2):103646. doi: 10.1016/j.ejmg.2019.04.003. Epub 2019 Apr 6.
• [4] Analysis of predicted loss-of-function variants in UK Biobank identifies variants protective for disease.Nat Commun. 2018 Apr 24;9(1):1613. doi: 10.1038/s41467-018-03911-8.
• [5] Modulation of Dengue/Zika Virus Pathogenicity by Antibody-Dependent Enhancement and Strategies to Protect Against Enhancement in Zika Virus Infection.Front Immunol. 2018 Apr 23;9:597. doi: 10.3389/fimmu.2018.00597. eCollection 2018.
• [6] Multicenter Prospective Study of the Efficacy and Safety of Combined Immunosuppressive Therapy With High-Dose Glucocorticoid, Tacrolimus, and Cyclophosphamide in Interstitial Lung Diseases Accompanied by Anti-Melanoma Differentiation-Associated Gene 5-Positive Dermatomyositis.Arthritis Rheumatol. 2020 Mar;72(3):488-498. doi: 10.1002/art.41105. Epub 2020 Jan 27.
• [7] Analysis of chosen polymorphisms rs2476601 a/G - PTPN22, rs1990760 C/T - IFIH1, rs179247 a/G - TSHR in pathogenesis of autoimmune thyroid diseases in children.Autoimmunity. 2018 Jun;51(4):183-190. doi: 10.1080/08916934.2018.1486824. Epub 2018 Jul 4.
• [8] Frequency, mutual exclusivity and clinical associations of myositis autoantibodies in a combined European cohort of idiopathic inflammatory myopathy patients.J Autoimmun. 2019 Jul;101:48-55. doi: 10.1016/j.jaut.2019.04.001. Epub 2019 Apr 13.
• [9] Recurrent rhinovirus infections in a child with inherited MDA5 deficiency.J Exp Med. 2017 Jul 3;214(7):1949-1972. doi: 10.1084/jem.20161759. Epub 2017 Jun 12.
• [10] The juvenile idiopathic inflammatory myopathies: pathogenesis, clinical and autoantibody phenotypes, and outcomes.J Intern Med. 2016 Jul;280(1):24-38. doi: 10.1111/joim.12444. Epub 2016 Mar 30.
• [11] Singleton-Merten Syndrome-like Skeletal Abnormalities in Mice with Constitutively Activated MDA5.J Immunol. 2019 Sep 1;203(5):1356-1368. doi: 10.4049/jimmunol.1900354. Epub 2019 Jul 31.
• [12] In vivo ligands of MDA5 and RIG-I in measles virus-infected cells.PLoS Pathog. 2014 Apr 17;10(4):e1004081. doi: 10.1371/journal.ppat.1004081. eCollection 2014 Apr.
• [13] Serum YKL-40 level is associated with severity of interstitial lung disease and poor prognosis in dermatomyositis with anti-MDA5 antibody.Clin Rheumatol. 2019 Jun;38(6):1655-1663. doi: 10.1007/s10067-019-04457-w. Epub 2019 Feb 9.
• [14] Innate immune sensor laboratory of genetics and physiology 2 suppresses tumor cell growth and functions as a prognostic marker in neuroblastoma.Cancer Sci. 2018 Nov;109(11):3494-3502. doi: 10.1111/cas.13790. Epub 2018 Oct 4.
• [15] A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.Nat Genet. 2010 Nov;42(11):985-90. doi: 10.1038/ng.694. Epub 2010 Oct 17.
• [16] Analysis of anti-melanoma differentiation-associated gene 5 antibody in Hong Kong Chinese patients with idiopathic inflammatory myopathies: diagnostic utility and clinical correlations.Int J Rheum Dis. 2018 May;21(5):1076-1081. doi: 10.1111/1756-185X.13268. Epub 2018 Jan 30.
• [17] Clinical features of patients with anti-melanoma differentiation-associated gene-5 antibody-positive dermatomyositis complicated by spontaneous pneumomediastinum.Clin Rheumatol. 2019 Dec;38(12):3443-3450. doi: 10.1007/s10067-019-04729-5. Epub 2019 Aug 16.
• [18] A specific IFIH1 gain-of-function mutation causes Singleton-Merten syndrome. Am J Hum Genet. 2015 Feb 5;96(2):275-82. doi: 10.1016/j.ajhg.2014.12.014. Epub 2015 Jan 22.
• [19] The relationship between type 1 IFN and vasculopathy in anti-MDA5 antibody-positive dermatomyositis patients.Rheumatology (Oxford). 2019 May 1;58(5):786-791. doi: 10.1093/rheumatology/key386.
• [20] Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo.Nat Genet. 2012 May 6;44(6):676-80. doi: 10.1038/ng.2272.
• [21] Insights into ZIKV-Mediated Innate Immune Responses in Human Dermal Fibroblasts and Epidermal Keratinocytes.J Invest Dermatol. 2019 Feb;139(2):391-399. doi: 10.1016/j.jid.2018.07.038. Epub 2018 Sep 12.
• [22] Deficient pulmonary IFN- expression in COPD patients.PLoS One. 2019 Jun 6;14(6):e0217803. doi: 10.1371/journal.pone.0217803. eCollection 2019.
• [23] Expression of Innate Immunity Genes in Epithelial Cells of Hypertrophic Adenoids with and without Pediatric Chronic Rhinosinusitis: A Preliminary Report.Chin Med J (Engl). 2015 Nov 5;128(21):2913-8. doi: 10.4103/0366-6999.168056.
• [24] The A allele of the rs1990760 polymorphism in the IFIH1 gene is associated with protection for arterial hypertension in type 1 diabetic patients and with expression of this gene in human mononuclear cells.PLoS One. 2013 Dec 27;8(12):e83451. doi: 10.1371/journal.pone.0083451. eCollection 2013.
• [25] Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.Nat Genet. 2015 Sep;47(9):979-986. doi: 10.1038/ng.3359. Epub 2015 Jul 20.
• [26] The interferon-induced helicase C domain-containing protein 1 gene variant (rs1990760) as an autoimmune-based pathology susceptibility factor.Immunobiology. 2020 Jan;225(1):151864. doi: 10.1016/j.imbio.2019.10.013. Epub 2019 Nov 5.
• [27] Gene-function studies in systemic lupus erythematosus.Curr Opin Rheumatol. 2019 Mar;31(2):185-192. doi: 10.1097/BOR.0000000000000572.
• [28] Polymorphisms in the interferon-induced helicase (IFIH1) locus and susceptibility to Addison's disease.Clin Endocrinol (Oxf). 2013 Feb;78(2):191-6. doi: 10.1111/j.1365-2265.2012.04497.x.
• [29] Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.Nat Genet. 2016 May;48(5):510-8. doi: 10.1038/ng.3528. Epub 2016 Mar 14.
• [30] Decreased A-to-I RNA editing as a source of keratinocytes' dsRNA in psoriasis.RNA. 2018 Jun;24(6):828-840. doi: 10.1261/rna.064659.117. Epub 2018 Mar 28.
• [31] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [32] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [33] 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.
• [34] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [35] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [36] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [37] 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.
• [38] 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.
• [39] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [40] Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
• [41] 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.
• [42] Hydroxychloroquine-inhibited dengue virus is associated with host defense machinery. J Interferon Cytokine Res. 2015 Mar;35(3):143-56. doi: 10.1089/jir.2014.0038. Epub 2014 Oct 16.
• [43] Integrated transcriptomic and metabolomic analyses to characterize the anti-cancer effects of (-)-epigallocatechin-3-gallate in human colon cancer cells. Toxicol Appl Pharmacol. 2020 Aug 15;401:115100. doi: 10.1016/j.taap.2020.115100. Epub 2020 Jun 6.
• [44] 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.
• [45] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [46] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [47] 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.
• [48] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [49] 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.
• [50] 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.