Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZF5X1D)

• DOT Name: Insulin-induced gene 1 protein (INSIG1)
• Synonyms: INSIG-1
• Gene Name: INSIG1
• Related Disease:
  Alzheimer disease
  Cytomegalovirus infection
  Fatty liver disease
  Gastric cancer
  Gastric neoplasm
  Non-alcoholic fatty liver disease
  Stomach cancer
  Coronary atherosclerosis
  Coronary heart disease
  Transposition of the great arteries
  Carcinoma
  Obesity
  Sickle-cell anaemia
  Systemic primary carnitine deficiency disease
  Undifferentiated carcinoma
• UniProt ID: INSI1_HUMAN
• PDB ID: 4J81
• Pfam ID: PF07281
• Sequence:
  MPRLHDHFWSCSCAHSARRRGPPRASAAGLAAKVGEMINVSVSGPSLLAAHGAPDADPAP
  RGRSAAMSGPEPGSPYPNTWHHRLLQRSLVLFSVGVVLALVLNLLQIQRNVTLFPEEVIA
  TIFSSAWWVPPCCGTAAAVVGLLYPCIDSHLGEPHKFKREWASVMRCIAVFVGINHASAK
  LDFANNVQLSLTLAALSLGLWWTFDRSRSGLGLGITIAFLATLITQFLVYNGVYQYTSPD
  FLYIRSWLPCIFFSGGVTVGNIGRQLAMGVPEKPHSD
• Function: Oxysterol-binding protein that mediates feedback control of cholesterol synthesis by controlling both endoplasmic reticulum to Golgi transport of SCAP and degradation of HMGCR. Acts as a negative regulator of cholesterol biosynthesis by mediating the retention of the SCAP-SREBP complex in the endoplasmic reticulum, thereby blocking the processing of sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2. Binds oxysterol, including 25-hydroxycholesterol, regulating interaction with SCAP and retention of the SCAP-SREBP complex in the endoplasmic reticulum. In presence of oxysterol, interacts with SCAP, retaining the SCAP-SREBP complex in the endoplasmic reticulum, thereby preventing SCAP from escorting SREBF1/SREBP1 and SREBF2/SREBP2 to the Golgi. Sterol deprivation or phosphorylation by PCK1 reduce oxysterol-binding, disrupting the interaction between INSIG1 and SCAP, thereby promoting Golgi transport of the SCAP-SREBP complex, followed by processing and nuclear translocation of SREBF1/SREBP1 and SREBF2/SREBP2. Also regulates cholesterol synthesis by regulating degradation of HMGCR: initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligases AMFR/gp78 and/or RNF139. Also regulates degradation of SOAT2/ACAT2 when the lipid levels are low: initiates the ubiquitin-mediated degradation of SOAT2/ACAT2 via recruitment of the ubiquitin ligases AMFR/gp78.
• Tissue Specificity: Expressed in all tissues tested with highest expression in the liver.
• Reactome Pathway: Regulation of cholesterol biosynthesis by SREBP (SREBF) (R-HSA-1655829)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Cytomegalovirus infection	DISCEMGC	Strong	Altered Expression	[2]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[3]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[4]
Gastric neoplasm	DISOKN4Y	Strong	Altered Expression	[4]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[3]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[4]
Coronary atherosclerosis	DISKNDYU	moderate	Genetic Variation	[5]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[5]
Transposition of the great arteries	DISPXJ8X	moderate	Genetic Variation	[5]
Carcinoma	DISH9F1N	Limited	Biomarker	[6]
Obesity	DIS47Y1K	Limited	Genetic Variation	[7]
Sickle-cell anaemia	DIS5YNZB	Limited	Genetic Variation	[8]
Systemic primary carnitine deficiency disease	DIS9OPZ4	Limited	Genetic Variation	[8]
Undifferentiated carcinoma	DISIAZST	Limited	Biomarker	[6]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Insulin-induced gene 1 protein (INSIG1) affects the response to substance of Etoposide.	[60]
Paclitaxel	DMLB81S	Approved	Insulin-induced gene 1 protein (INSIG1) affects the response to substance of Paclitaxel.	[60]
Topotecan	DMP6G8T	Approved	Insulin-induced gene 1 protein (INSIG1) affects the response to substance of Topotecan.	[60]

1 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 Insulin-induced gene 1 protein (INSIG1).	[9]

62 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 Insulin-induced gene 1 protein (INSIG1).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Insulin-induced gene 1 protein (INSIG1).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[15]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Insulin-induced gene 1 protein (INSIG1).	[16]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[17]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[18]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Insulin-induced gene 1 protein (INSIG1).	[19]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[20]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Insulin-induced gene 1 protein (INSIG1).	[19]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Insulin-induced gene 1 protein (INSIG1).	[21]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[22]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Insulin-induced gene 1 protein (INSIG1).	[23]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Insulin-induced gene 1 protein (INSIG1).	[24]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Insulin-induced gene 1 protein (INSIG1).	[25]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Insulin-induced gene 1 protein (INSIG1).	[26]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[27]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[28]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[28]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Insulin-induced gene 1 protein (INSIG1).	[29]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[30]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Insulin-induced gene 1 protein (INSIG1).	[31]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[32]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[33]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Insulin-induced gene 1 protein (INSIG1).	[34]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Insulin-induced gene 1 protein (INSIG1).	[35]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Insulin-induced gene 1 protein (INSIG1).	[36]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Insulin-induced gene 1 protein (INSIG1).	[25]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[28]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Insulin-induced gene 1 protein (INSIG1).	[36]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Insulin-induced gene 1 protein (INSIG1).	[37]
Lovastatin	DM9OZWQ	Approved	Lovastatin increases the expression of Insulin-induced gene 1 protein (INSIG1).	[38]
Crizotinib	DM4F29C	Approved	Crizotinib increases the expression of Insulin-induced gene 1 protein (INSIG1).	[39]
Vandetanib	DMRICNP	Approved	Vandetanib increases the expression of Insulin-induced gene 1 protein (INSIG1).	[40]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Insulin-induced gene 1 protein (INSIG1).	[41]
Isoflavone	DM7U58J	Phase 4	Isoflavone increases the expression of Insulin-induced gene 1 protein (INSIG1).	[42]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[20]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Insulin-induced gene 1 protein (INSIG1).	[43]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[44]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Insulin-induced gene 1 protein (INSIG1).	[45]
T83193	DMHO29Y	Patented	T83193 decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[46]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[47]
Celastrol	DMWQIJX	Preclinical	Celastrol increases the expression of Insulin-induced gene 1 protein (INSIG1).	[48]
UNC0379	DMD1E4J	Preclinical	UNC0379 increases the expression of Insulin-induced gene 1 protein (INSIG1).	[49]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Insulin-induced gene 1 protein (INSIG1).	[50]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Insulin-induced gene 1 protein (INSIG1).	[51]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[52]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Insulin-induced gene 1 protein (INSIG1).	[53]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Insulin-induced gene 1 protein (INSIG1).	[16]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Insulin-induced gene 1 protein (INSIG1).	[54]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Insulin-induced gene 1 protein (INSIG1).	[18]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[46]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Insulin-induced gene 1 protein (INSIG1).	[54]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[55]
Linalool	DMGZQ5P	Investigative	Linalool increases the expression of Insulin-induced gene 1 protein (INSIG1).	[56]
GW7647	DM9RD0C	Investigative	GW7647 increases the expression of Insulin-induced gene 1 protein (INSIG1).	[57]
GW-3965	DMG60ET	Investigative	GW-3965 increases the expression of Insulin-induced gene 1 protein (INSIG1).	[57]
Ganoderic acid A	DM42EVG	Investigative	Ganoderic acid A decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[58]
SC-560	DMT1GJL	Investigative	SC-560 decreases the expression of Insulin-induced gene 1 protein (INSIG1).	[59]

References

• [1] Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer's disease with OSBPL6, PTPRG, and PDCL3.Mol Psychiatry. 2016 Nov;21(11):1608-1612. doi: 10.1038/mp.2015.218. Epub 2016 Feb 2.
• [2] PKR-like endoplasmic reticulum kinase is necessary for lipogenic activation during HCMV infection.PLoS Pathog. 2013;9(4):e1003266. doi: 10.1371/journal.ppat.1003266. Epub 2013 Apr 4.
• [3] Inhibition of microRNA-24 expression in liver prevents hepatic lipid accumulation and hyperlipidemia.Hepatology. 2014 Aug;60(2):554-64. doi: 10.1002/hep.27153. Epub 2014 May 19.
• [4] Reduced expression of the insulin-induced protein 1 and p41 Arp2/3 complex genes in human gastric cancers.Int J Cancer. 2002 Jul 1;100(1):57-62. doi: 10.1002/ijc.10464.
• [5] The INSIG1 gene, not the INSIG2 gene, associated with coronary heart disease: tagSNPs and haplotype-based association study. The Beijing Atherosclerosis Study.Thromb Haemost. 2008 Nov;100(5):886-92.
• [6] cDNA microarray profiling of rat mammary gland carcinomas induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 7,12-dimethylbenz[a]anthracene.Carcinogenesis. 2002 Oct;23(10):1561-8. doi: 10.1093/carcin/23.10.1561.
• [7] Investigation of the association between obesity and insulin-induced gene 1 polymorphism at 7q36.3 region in Uygur population in Xinjiang, China.Biosci Rep. 2019 Dec 20;39(12):BSR20190498. doi: 10.1042/BSR20190498.
• [8] Schnyder corneal dystrophy-associated UBIAD1 mutations cause corneal cholesterol accumulation by stabilizing HMG-CoA reductase.PLoS Genet. 2019 Jul 19;15(7):e1008289. doi: 10.1371/journal.pgen.1008289. eCollection 2019 Jul.
• [9] 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.
• [10] 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.
• [11] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
• [12] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [13] 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.
• [14] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [15] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [16] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [17] 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.
• [18] MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.
• [19] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [20] 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.
• [21] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [22] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [23] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [24] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [25] 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.
• [26] Impact of extracellular folate levels on global gene expression. Mol Pharmacol. 2001 Dec;60(6):1288-95. doi: 10.1124/mol.60.6.1288.
• [27] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [28] 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.
• [29] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [30] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [31] In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Toxicol In Vitro. 2013 Apr;27(3):1072-81.
• [32] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [33] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [34] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [35] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [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] Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics. Sci Rep. 2023 Jun 29;13(1):10519. doi: 10.1038/s41598-023-37488-0.
• [38] Desmosterol can replace cholesterol in sustaining cell proliferation and regulating the SREBP pathway in a sterol-Delta24-reductase-deficient cell line. Biochem J. 2009 May 13;420(2):305-15.
• [39] Multi-parameter in vitro toxicity testing of crizotinib, sunitinib, erlotinib, and nilotinib in human cardiomyocytes. Toxicol Appl Pharmacol. 2013 Oct 1;272(1):245-55.
• [40] ZD6474 inhibits tumor growth and intraperitoneal dissemination in a highly metastatic orthotopic gastric cancer model. Int J Cancer. 2006 Jan 15;118(2):483-9. doi: 10.1002/ijc.21340.
• [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] Soy isoflavones exert differential effects on androgen responsive genes in LNCaP human prostate cancer cells. J Nutr. 2007 Apr;137(4):964-72.
• [43] The molecular basis of genistein-induced mitotic arrest and exit of self-renewal in embryonal carcinoma and primary cancer cell lines. BMC Med Genomics. 2008 Oct 10;1:49.
• [44] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [45] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [46] Antimutagenicity of cinnamaldehyde and vanillin in human cells: Global gene expression and possible role of DNA damage and repair. Mutat Res. 2007 Mar 1;616(1-2):60-9. doi: 10.1016/j.mrfmmm.2006.11.022. Epub 2006 Dec 18.
• [47] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [48] Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell. 2006 Oct;10(4):321-30.
• [49] Epigenetic siRNA and chemical screens identify SETD8 inhibition as a therapeutic strategy for p53 activation in high-risk neuroblastoma. Cancer Cell. 2017 Jan 9;31(1):50-63.
• [50] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [51] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [52] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [53] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [54] Identification of genes targeted by the androgen and PKA signaling pathways in prostate cancer cells. Oncogene. 2006 Nov 23;25(55):7311-23.
• [55] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.
• [56] Linalool reduces the expression of 3-hydroxy-3-methylglutaryl CoA reductase via sterol regulatory element binding protein-2- and ubiquitin-dependent mechanisms. FEBS Lett. 2011 Oct 20;585(20):3289-96.
• [57] System analysis of cross-talk between nuclear receptors reveals an opposite regulation of the cell cycle by LXR and FXR in human HepaRG liver cells. PLoS One. 2019 Aug 22;14(8):e0220894. doi: 10.1371/journal.pone.0220894. eCollection 2019.
• [58] Ganoderic Acid A improves high fat diet-induced obesity, lipid accumulation and insulin sensitivity through regulating SREBP pathway. Chem Biol Interact. 2018 Jun 25;290:77-87.
• [59] Gene modulation by Cox-1 and Cox-2 specific inhibitors in human colorectal carcinoma cancer cells. Carcinogenesis. 2004 Mar;25(3):349-57.
• [60] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.