Details of Drug Off-Target (DOT)

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

• DOT Name: Syndecan-4 (SDC4)
• Synonyms: SYND4; Amphiglycan; Ryudocan core protein
• Gene Name: SDC4
• Related Disease:
  Thyroid gland papillary carcinoma
  Acute myocardial infarction
  Arteriosclerosis
  Arthritis
  Astrocytoma
  Atherosclerosis
  Autism spectrum disorder
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cardiac failure
  Chagas disease
  Chronic obstructive pulmonary disease
  Colitis
  Colon cancer
  Colon carcinoma
  Congestive heart failure
  Dilated cardiomyopathy 1A
  Early-onset anterior polar cataract
  Endometriosis
  Hepatitis C virus infection
  Hyperglycemia
  Knee osteoarthritis
  Melanoma
  Mycobacterium infection
  Nephropathy
  Non-small-cell lung cancer
  Osteoarthritis
  Osteosarcoma
  Pneumonia
  Pneumonitis
  Pulmonary fibrosis
  Rheumatoid arthritis
  Synovitis
  Thyroid gland carcinoma
  Type-1/2 diabetes
  Advanced cancer
  Acute myelogenous leukaemia
  Aortic valve stenosis
  Asthma
  Bacterial infection
  Myocardial infarction
  Neoplasm
  Primary cutaneous T-cell lymphoma
  Sezary syndrome
  Skin disease
  Stroke
• UniProt ID: SDC4_HUMAN
• PDB ID: 1EJP; 1EJQ; 1OBY; 1YBO; 8BLV
• Pfam ID: PF01034
• Sequence:
  MAPARLFALLLFFVGGVAESIRETEVIDPQDLLEGRYFSGALPDDEDVVGPGQESDDFEL
  SGSGDLDDLEDSMIGPEVVHPLVPLDNHIPERAGSGSQVPTEPKKLEENEVIPKRISPVE
  ESEDVSNKVSMSSTVQGSNIFERTEVLAALIVGGIVGILFAVFLILLLMYRMKKKDEGSY
  DLGKKPIYKKAPTNEFYA
• Function: Cell surface proteoglycan which regulates exosome biogenesis in concert with SDCBP and PDCD6IP.
• Tissue Specificity: Detected in fibroblasts (at protein level) . Also expressed in epithelial cells .
• KEGG Pathway:
  ECM-receptor interaction (hsa04512)
  Cell adhesion molecules (hsa04514)
  Cytoskeleton in muscle cells (hsa04820)
  Proteoglycans in cancer (hsa05205)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  HS-GAG biosynthesis (R-HSA-2022928)
  HS-GAG degradation (R-HSA-2024096)
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Syndecan interactions (R-HSA-3000170)
  Defective B4GALT7 causes EDS, progeroid type (R-HSA-3560783)
  Defective B3GAT3 causes JDSSDHD (R-HSA-3560801)
  Defective EXT2 causes exostoses 2 (R-HSA-3656237)
  Defective EXT1 causes exostoses 1, TRPS2 and CHDS (R-HSA-3656253)
  Defective B3GALT6 causes EDSP2 and SEMDJL1 (R-HSA-4420332)
  Attachment and Entry (R-HSA-9694614)
  Retinoid metabolism and transport (R-HSA-975634)
  A tetrasaccharide linker sequence is required for GAG synthesis (R-HSA-1971475)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Altered Expression	[1]
Acute myocardial infarction	DISE3HTG	Strong	Altered Expression	[2]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[3]
Arthritis	DIST1YEL	Strong	Biomarker	[4]
Astrocytoma	DISL3V18	Strong	Biomarker	[5]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[3]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[6]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[9]
Cardiac failure	DISDC067	Strong	Biomarker	[10]
Chagas disease	DIS8KNVF	Strong	Biomarker	[2]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Altered Expression	[11]
Colitis	DISAF7DD	Strong	Biomarker	[4]
Colon cancer	DISVC52G	Strong	Altered Expression	[12]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[12]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[10]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[13]
Early-onset anterior polar cataract	DISTOPIY	Strong	Biomarker	[14]
Endometriosis	DISX1AG8	Strong	Altered Expression	[15]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[16]
Hyperglycemia	DIS0BZB5	Strong	Biomarker	[17]
Knee osteoarthritis	DISLSNBJ	Strong	Biomarker	[18]
Melanoma	DIS1RRCY	Strong	Altered Expression	[19]
Mycobacterium infection	DISNSMUD	Strong	Altered Expression	[20]
Nephropathy	DISXWP4P	Strong	Biomarker	[21]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[22]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[23]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[7]
Pneumonia	DIS8EF3M	Strong	Biomarker	[24]
Pneumonitis	DIS88E0K	Strong	Biomarker	[24]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[24]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[25]
Synovitis	DISW2GPY	Strong	Biomarker	[26]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[27]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[17]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[28]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[29]
Aortic valve stenosis	DISW7AQ9	Limited	Biomarker	[30]
Asthma	DISW9QNS	Limited	Altered Expression	[31]
Bacterial infection	DIS5QJ9S	Limited	Biomarker	[32]
Myocardial infarction	DIS655KI	Limited	Biomarker	[33]
Neoplasm	DISZKGEW	Limited	Altered Expression	[34]
Primary cutaneous T-cell lymphoma	DIS35WVW	Limited	Altered Expression	[35]
Sezary syndrome	DISFMTC7	Limited	Biomarker	[35]
Skin disease	DISDW8R6	Limited	Altered Expression	[35]
Stroke	DISX6UHX	Limited	Altered Expression	[36]

30 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 Syndecan-4 (SDC4).	[37]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Syndecan-4 (SDC4).	[38]
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Syndecan-4 (SDC4).	[39]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Syndecan-4 (SDC4).	[40]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Syndecan-4 (SDC4).	[41]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Syndecan-4 (SDC4).	[42]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Syndecan-4 (SDC4).	[43]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Syndecan-4 (SDC4).	[45]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Syndecan-4 (SDC4).	[46]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Syndecan-4 (SDC4).	[47]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Syndecan-4 (SDC4).	[48]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Syndecan-4 (SDC4).	[49]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Syndecan-4 (SDC4).	[50]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Syndecan-4 (SDC4).	[51]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Syndecan-4 (SDC4).	[52]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Syndecan-4 (SDC4).	[53]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Syndecan-4 (SDC4).	[54]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Syndecan-4 (SDC4).	[55]
Ardeparin	DMYRX8B	Approved	Ardeparin increases the expression of Syndecan-4 (SDC4).	[56]
Epanova	DMHEAGL	Approved	Epanova increases the expression of Syndecan-4 (SDC4).	[57]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Syndecan-4 (SDC4).	[58]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate decreases the expression of Syndecan-4 (SDC4).	[59]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Syndecan-4 (SDC4).	[61]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Syndecan-4 (SDC4).	[62]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Syndecan-4 (SDC4).	[63]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Syndecan-4 (SDC4).	[65]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Syndecan-4 (SDC4).	[66]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Syndecan-4 (SDC4).	[67]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Syndecan-4 (SDC4).	[68]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Syndecan-4 (SDC4).	[69]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the ubiquitination of Syndecan-4 (SDC4).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Syndecan-4 (SDC4).	[60]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Syndecan-4 (SDC4).	[64]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Apratastat	DM8W4N9	Phase 2	Apratastat decreases the secretion of Syndecan-4 (SDC4).	[59]

References

• [1] SDC4 Gene Silencing Favors Human Papillary Thyroid Carcinoma Cell Apoptosis and Inhibits Epithelial Mesenchymal Transition via Wnt/-Catenin Pathway.Mol Cells. 2018 Sep 30;41(9):853-867. doi: 10.14348/molcells.2018.0103. Epub 2018 Aug 31.
• [2] Lack of association between serum syndecan-4, myocardial fibrosis and ventricular dysfunction in subjects with chronic Chagas disease.PLoS One. 2017 Dec 12;12(12):e0189408. doi: 10.1371/journal.pone.0189408. eCollection 2017.
• [3] miR-126 Is Involved in Vascular Remodeling under Laminar Shear Stress.Biomed Res Int. 2015;2015:497280. doi: 10.1155/2015/497280. Epub 2015 Jun 28.
• [4] Syndecan-4 Modulates Epithelial Gut Barrier Function and Epithelial Regeneration in Experimental Colitis.Inflamm Bowel Dis. 2018 Nov 29;24(12):2579-2589. doi: 10.1093/ibd/izy248.
• [5] Circulating microRNAs as Biomarkers for Pediatric Astrocytomas.Arch Med Res. 2017 May;48(4):323-332. doi: 10.1016/j.arcmed.2017.07.002.
• [6] Integrated Transcriptome Analyses Revealed Key Target Genes in Mouse Models of Autism.Autism Res. 2020 Mar;13(3):352-368. doi: 10.1002/aur.2240. Epub 2019 Nov 19.
• [7] Differential regulation of syndecan expression by osteosarcoma cell lines in response to cytokines but not osteotropic hormones.Bone. 1999 Jun;24(6):571-8. doi: 10.1016/s8756-3282(99)00088-5.
• [8] Sulfated Glycoaminoglycans and Proteoglycan Syndecan-4 Are Involved in Membrane Fixation of LL-37 and Its Pro-Migratory Effect in Breast Cancer Cells.Biomolecules. 2019 Sep 12;9(9):481. doi: 10.3390/biom9090481.
• [9] Association of heparan sulfate proteoglycans SDC1 and SDC4 polymorphisms with breast cancer in an Australian Caucasian population.Tumour Biol. 2015 Mar;36(3):1731-8. doi: 10.1007/s13277-014-2774-3. Epub 2014 Nov 1.
• [10] Syndecan-4 deficiency accelerates the transition from compensated hypertrophy to heart failure following pressure overload.Cardiovasc Pathol. 2017 May-Jun;28:74-79. doi: 10.1016/j.carpath.2017.03.008. Epub 2017 Mar 30.
• [11] Circulating syndecan-1 as a novel biomarker relates to lung function, systemic inflammation, and exacerbation in COPD.Int J Chron Obstruct Pulmon Dis. 2019 Aug 28;14:1933-1941. doi: 10.2147/COPD.S207855. eCollection 2019.
• [12] Expression of matrix macromolecules and functional properties of EGF-responsive colon cancer cells are inhibited by panitumumab.Invest New Drugs. 2013 Jun;31(3):516-24. doi: 10.1007/s10637-012-9875-x. Epub 2012 Sep 6.
• [13] Differences in biochemical and genetic biomarkers in patients with heart failure of various etiologies.Int J Cardiol. 2016 Oct 15;221:1073-80. doi: 10.1016/j.ijcard.2016.07.150. Epub 2016 Jul 12.
• [14] Serum suPAR and syndecan-4 levels predict severity of community-acquired pneumonia: a prospective, multi-centre study.Crit Care. 2018 Jan 24;22(1):15. doi: 10.1186/s13054-018-1943-y.
• [15] Syndecan-4 expression is upregulated in endometriosis and contributes to an invasive phenotype.Fertil Steril. 2016 Aug;106(2):378-85. doi: 10.1016/j.fertnstert.2016.03.032. Epub 2016 Mar 31.
• [16] Attachment and Postattachment Receptors Important for Hepatitis C Virus Infection and Cell-to-Cell Transmission.J Virol. 2017 Jun 9;91(13):e00280-17. doi: 10.1128/JVI.00280-17. Print 2017 Jul 1.
• [17] Matrix metalloproteinase-9 mediated shedding of syndecan-4 in glomerular endothelial cells.Microcirculation. 2019 Jan 31:e12534. doi: 10.1111/micc.12534. Online ahead of print.
• [18] Syndecan-4 Is Increased in Osteoarthritic Knee, but Not Hip or Shoulder, Articular Hypertrophic Chondrocytes.Cartilage. 2021 Dec;13(2_suppl):862S-871S. doi: 10.1177/1947603519870855. Epub 2019 Aug 27.
• [19] Fibroblast growth factor-2 modulates melanoma adhesion and migration through a syndecan-4-dependent mechanism.Int J Biochem Cell Biol. 2009 Jun;41(6):1323-31. doi: 10.1016/j.biocel.2008.11.008. Epub 2008 Dec 6.
• [20] Syndecans promote mycobacterial internalization by lung epithelial cells.Cell Microbiol. 2016 Dec;18(12):1846-1856. doi: 10.1111/cmi.12627. Epub 2016 Jul 15.
• [21] Tissue-resident natural killer cells exacerbate tubulointerstitial fibrosis by activating transglutaminase 2 and syndecan-4 in a model of aristolochic acid-induced nephropathy.BMB Rep. 2019 Sep;52(9):554-559. doi: 10.5483/BMBRep.2019.52.9.193.
• [22] Concurrent ROS1 gene rearrangement and KRAS mutation in lung adenocarcinoma: A case report and literature review.Thorac Cancer. 2018 Jan;9(1):159-163. doi: 10.1111/1759-7714.12518. Epub 2017 Oct 3.
• [23] Osthole ameliorates cartilage degradation by downregulation of NF-B and HIF-2 pathways in an osteoarthritis murine model.Eur J Pharmacol. 2020 Jan 15;867:172799. doi: 10.1016/j.ejphar.2019.172799. Epub 2019 Nov 22.
• [24] Syndecan-4 Inhibits the Development of Pulmonary Fibrosis by Attenuating TGF- Signaling.Int J Mol Sci. 2019 Oct 9;20(20):4989. doi: 10.3390/ijms20204989.
• [25] Syndecan-4 involves in the pathogenesis of rheumatoid arthritis by regulating the inflammatory response and apoptosis of fibroblast-like synoviocytes.J Cell Physiol. 2020 Feb;235(2):1746-1758. doi: 10.1002/jcp.29093. Epub 2019 Jul 15.
• [26] Inflammation in osteoarthritis.Curr Opin Rheumatol. 2011 Sep;23(5):471-8. doi: 10.1097/BOR.0b013e328349c2b1.
• [27] Identification of novel diagnostic biomarkers for thyroid carcinoma.Oncotarget. 2017 Dec 4;8(67):111551-111566. doi: 10.18632/oncotarget.22873. eCollection 2017 Dec 19.
• [28] Autotaxin- interaction with the cell surface via syndecan-4 impacts on cancer cell proliferation and metastasis.Oncotarget. 2018 Sep 4;9(69):33170-33185. doi: 10.18632/oncotarget.26039. eCollection 2018 Sep 4.
• [29] Methylation profiling in acute myeloid leukemia.Blood. 2001 May 1;97(9):2823-9. doi: 10.1182/blood.v97.9.2823.
• [30] Symptom Onset in Aortic Stenosis: Relation to Sex Differences in Left Ventricular Remodeling.JACC Cardiovasc Imaging. 2019 Jan;12(1):96-105. doi: 10.1016/j.jcmg.2017.09.019. Epub 2017 Dec 13.
• [31] Th1 cytokine-induced syndecan-4 shedding by airway smooth muscle cells is dependent on mitogen-activated protein kinases.Am J Physiol Lung Cell Mol Physiol. 2012 Apr 1;302(7):L700-10. doi: 10.1152/ajplung.00167.2011. Epub 2012 Jan 20.
• [32] Role of Syndecan-4 in the cellular invasion of Orientia tsutsugamushi.Microb Pathog. 2004 Apr;36(4):219-25. doi: 10.1016/j.micpath.2003.12.005.
• [33] Gender differences in the association of syndecan-4 with myocardial infarction: The population-based Troms Study.Atherosclerosis. 2018 Nov;278:166-173. doi: 10.1016/j.atherosclerosis.2018.08.005. Epub 2018 Sep 15.
• [34] Targeting of CCL2-CCR2-Glycosaminoglycan Axis Using a CCL2 Decoy Protein Attenuates Metastasis through Inhibition of Tumor Cell Seeding.Neoplasia. 2016 Jan;18(1):49-59. doi: 10.1016/j.neo.2015.11.013.
• [35] Szary syndrome cells overexpress syndecan-4 bearing distinct heparan sulfate moieties that suppress T-cell activation by binding DC-HIL and trapping TGF-beta on the cell surface.Blood. 2011 Mar 24;117(12):3382-90. doi: 10.1182/blood-2010-08-302034. Epub 2011 Jan 20.
• [36] The potential role of inflammation in cryptogenic stroke.Adv Med Sci. 2019 Sep;64(2):381-387. doi: 10.1016/j.advms.2019.06.001. Epub 2019 Jun 28.
• [37] 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.
• [38] 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.
• [39] Molecular characterization of a toxicological tipping point during human stem cell differentiation. Reprod Toxicol. 2020 Jan;91:1-13. doi: 10.1016/j.reprotox.2019.10.001. Epub 2019 Oct 7.
• [40] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [41] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [42] Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks. Mutagenesis. 2014 Jan;29(1):17-26.
• [43] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [44] Quantitative Assessment of Arsenite-Induced Perturbation of Ubiquitinated Proteome. Chem Res Toxicol. 2022 Sep 19;35(9):1589-1597. doi: 10.1021/acs.chemrestox.2c00197. Epub 2022 Aug 22.
• [45] 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.
• [46] 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.
• [47] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [48] Novel functional view of the crocidolite asbestos-treated A549 human lung epithelial transcriptome reveals an intricate network of pathways with opposing functions. BMC Genomics. 2008 Aug 7;9:376.
• [49] The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet. 2009 Feb;41(2):178-186.
• [50] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [51] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [52] 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.
• [53] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [54] 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.
• [55] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [56] Biochemical and toxicological evaluation of nano-heparins in cell functional properties, proteasome activation and expression of key matrix molecules. Toxicol Lett. 2016 Jan 5;240(1):32-42. doi: 10.1016/j.toxlet.2015.10.005. Epub 2015 Oct 22.
• [57] Differential effects of omega-3 and omega-6 Fatty acids on gene expression in breast cancer cells. Breast Cancer Res Treat. 2007 Jan;101(1):7-16. doi: 10.1007/s10549-006-9269-x. Epub 2006 Jul 6.
• [58] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [59] A disintegrin and metalloproteinase 17 (ADAM17) mediates inflammation-induced shedding of syndecan-1 and -4 by lung epithelial cells. J Biol Chem. 2010 Jan 1;285(1):555-64. doi: 10.1074/jbc.M109.059394. Epub 2009 Oct 29.
• [60] 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.
• [61] 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.
• [62] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [63] 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.
• [64] 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.
• [65] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [66] 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.
• [67] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [68] 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.
• [69] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.