Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ8FFNS)

• DOT Name: Sortilin-related receptor (SORL1)
• Synonyms: Low-density lipoprotein receptor relative with 11 ligand-binding repeats; LDLR relative with 11 ligand-binding repeats; LR11; SorLA-1; Sorting protein-related receptor containing LDLR class A repeats; SorLA
• Gene Name: SORL1
• Related Disease:
  Acute leukaemia
  Acute lymphocytic leukaemia
  Acute myelogenous leukaemia
  Childhood acute lymphoblastic leukemia
  Multiple sclerosis
  Advanced cancer
  Amyloidosis
  Bipolar disorder
  Cardiovascular disease
  Carotid stenosis
  Cerebrovascular disease
  Cholestasis
  Depression
  Familial hypercholesterolemia
  Huntington disease
  Hypercholesterolemia, familial, 1
  Obesity
  Parkinson disease
  Plasma cell myeloma
  Pulmonary arterial hypertension
  Schizophrenia
  Urinary bladder cancer
  Vascular disease
  Arteriosclerosis
  Atherosclerosis
  Atrial fibrillation
  Familial Alzheimer disease
  Familial atrial fibrillation
  Neuroblastoma
  Type-1/2 diabetes
  Early-onset autosomal dominant Alzheimer disease
  High blood pressure
  Non-insulin dependent diabetes
• UniProt ID: SORL_HUMAN
• PDB ID: 2DM4; 3G2S; 3G2T; 3WSX; 3WSY; 3WSZ; 7VT0
• Pfam ID: PF00041 ; PF00057 ; PF00058 ; PF15902 ; PF15901
• Sequence:
  MATRSSRRESRLPFLFTLVALLPPGALCEVWTQRLHGGSAPLPQDRGFLVVQGDPRELRL
  WARGDARGASRADEKPLRRKRSAALQPEPIKVYGQVSLNDSHNQMVVHWAGEKSNVIVAL
  ARDSLALARPKSSDVYVSYDYGKSFKKISDKLNFGLGNRSEAVIAQFYHSPADNKRYIFA
  DAYAQYLWITFDFCNTLQGFSIPFRAADLLLHSKASNLLLGFDRSHPNKQLWKSDDFGQT
  WIMIQEHVKSFSWGIDPYDKPNTIYIERHEPSGYSTVFRSTDFFQSRENQEVILEEVRDF
  QLRDKYMFATKVVHLLGSEQQSSVQLWVSFGRKPMRAAQFVTRHPINEYYIADASEDQVF
  VCVSHSNNRTNLYISEAEGLKFSLSLENVLYYSPGGAGSDTLVRYFANEPFADFHRVEGL
  QGVYIATLINGSMNEENMRSVITFDKGGTWEFLQAPAFTGYGEKINCELSQGCSLHLAQR
  LSQLLNLQLRRMPILSKESAPGLIIATGSVGKNLASKTNVYISSSAGARWREALPGPHYY
  TWGDHGGIITAIAQGMETNELKYSTNEGETWKTFIFSEKPVFVYGLLTEPGEKSTVFTIF
  GSNKENVHSWLILQVNATDALGVPCTENDYKLWSPSDERGNECLLGHKTVFKRRTPHATC
  FNGEDFDRPVVVSNCSCTREDYECDFGFKMSEDLSLEVCVPDPEFSGKSYSPPVPCPVGS
  TYRRTRGYRKISGDTCSGGDVEARLEGELVPCPLAEENEFILYAVRKSIYRYDLASGATE
  QLPLTGLRAAVALDFDYEHNCLYWSDLALDVIQRLCLNGSTGQEVIINSGLETVEALAFE
  PLSQLLYWVDAGFKKIEVANPDGDFRLTIVNSSVLDRPRALVLVPQEGVMFWTDWGDLKP
  GIYRSNMDGSAAYHLVSEDVKWPNGISVDDQWIYWTDAYLECIERITFSGQQRSVILDNL
  PHPYAIAVFKNEIYWDDWSQLSIFRASKYSGSQMEILANQLTGLMDMKIFYKGKNTGSNA
  CVPRPCSLLCLPKANNSRSCRCPEDVSSSVLPSGDLMCDCPQGYQLKNNTCVKQENTCLR
  NQYRCSNGNCINSIWWCDFDNDCGDMSDERNCPTTICDLDTQFRCQESGTCIPLSYKCDL
  EDDCGDNSDESHCEMHQCRSDEYNCSSGMCIRSSWVCDGDNDCRDWSDEANCTAIYHTCE
  ASNFQCRNGHCIPQRWACDGDTDCQDGSDEDPVNCEKKCNGFRCPNGTCIPSSKHCDGLR
  DCSDGSDEQHCEPLCTHFMDFVCKNRQQCLFHSMVCDGIIQCRDGSDEDAAFAGCSQDPE
  FHKVCDEFGFQCQNGVCISLIWKCDGMDDCGDYSDEANCENPTEAPNCSRYFQFRCENGH
  CIPNRWKCDRENDCGDWSDEKDCGDSHILPFSTPGPSTCLPNYYRCSSGTCVMDTWVCDG
  YRDCADGSDEEACPLLANVTAASTPTQLGRCDRFEFECHQPKTCIPNWKRCDGHQDCQDG
  RDEANCPTHSTLTCMSREFQCEDGEACIVLSERCDGFLDCSDESDEKACSDELTVYKVQN
  LQWTADFSGDVTLTWMRPKKMPSASCVYNVYYRVVGESIWKTLETHSNKTNTVLKVLKPD
  TTYQVKVQVQCLSKAHNTNDFVTLRTPEGLPDAPRNLQLSLPREAEGVIVGHWAPPIHTH
  GLIREYIVEYSRSGSKMWASQRAASNFTEIKNLLVNTLYTVRVAAVTSRGIGNWSDSKSI
  TTIKGKVIPPPDIHIDSYGENYLSFTLTMESDIKVNGYVVNLFWAFDTHKQERRTLNFRG
  SILSHKVGNLTAHTSYEISAWAKTDLGDSPLAFEHVMTRGVRPPAPSLKAKAINQTAVEC
  TWTGPRNVVYGIFYATSFLDLYRNPKSLTTSLHNKTVIVSKDEQYLFLVRVVVPYQGPSS
  DYVVVKMIPDSRLPPRHLHVVHTGKTSVVIKWESPYDSPDQDLLYAVAVKDLIRKTDRSY
  KVKSRNSTVEYTLNKLEPGGKYHIIVQLGNMSKDSSIKITTVSLSAPDALKIITENDHVL
  LFWKSLALKEKHFNESRGYEIHMFDSAMNITAYLGNTTDNFFKISNLKMGHNYTFTVQAR
  CLFGNQICGEPAILLYDELGSGADASATQAARSTDVAAVVVPILFLILLSLGVGFAILYT
  KHRRLQSSFTAFANSHYSSRLGSAIFSSGDDLGEDDEDAPMITGFSDDVPMVIA
• Function: Sorting receptor that directs several proteins to their correct location within the cell (Probable). Along with AP-1 complex, involved Golgi apparatus - endosome sorting. Sorting receptor for APP, regulating its intracellular trafficking and processing into amyloidogenic-beta peptides. Retains APP in the trans-Golgi network, hence preventing its transit through late endosomes where amyloid beta peptides Abeta40 and Abeta42 are generated. May also sort newly produced amyloid-beta peptides to lysosomes for catabolism. Does not affect APP trafficking from the endoplasmic reticulum to Golgi compartments. Sorting receptor for the BDNF receptor NTRK2/TRKB that facilitates NTRK2 trafficking between synaptic plasma membranes, postsynaptic densities and cell soma, hence positively regulates BDNF signaling by controlling the intracellular location of its receptor. Sorting receptor for GDNF that promotes GDNF regulated, but not constitutive secretion. Sorting receptor for the GDNF-GFRA1 complex, directing it from the cell surface to endosomes. GDNF is then targeted to lysosomes and degraded, while its receptor GFRA1 recycles back to the cell membrane, resulting in a GDNF clearance pathway. The SORL1-GFRA1 complex further targets RET for endocytosis, but not for degradation, affecting GDNF-induced neurotrophic activities. Sorting receptor for ERBB2/HER2. Regulates ERBB2 subcellular distribution by promoting its recycling after internalization from endosomes back to the plasma membrane, hence stimulating phosphoinositide 3-kinase (PI3K)-dependent ERBB2 signaling. In ERBB2-dependent cancer cells, promotes cell proliferation. Sorting receptor for lipoprotein lipase LPL. Promotes LPL localization to endosomes and later to the lysosomes, leading to degradation of newly synthesized LPL. Potential sorting receptor for APOA5, inducing APOA5 internalization to early endosomes, then to late endosomes, wherefrom a portion is sent to lysosomes and degradation, another portion is sorted to the trans-Golgi network. Sorting receptor for the insulin receptor INSR. Promotes recycling of internalized INSR via the Golgi apparatus back to the cell surface, thereby preventing lysosomal INSR catabolism, increasing INSR cell surface expression and strengthening insulin signal reception in adipose tissue. Does not affect INSR internalization. Plays a role in renal ion homeostasis, controlling the phospho-regulation of SLC12A1/NKCC2 by STK39/SPAK kinase and PPP3CB/calcineurin A beta phosphatase, possibly through intracellular sorting of STK39 and PPP3CB. Stimulates, via the N-terminal ectodomain, the proliferation and migration of smooth muscle cells, possibly by increasing cell surface expression of the urokinase receptor uPAR/PLAUR. This may promote extracellular matrix proteolysis and hence facilitate cell migration. By acting on the migration of intimal smooth muscle cells, may accelerate intimal thickening following vascular injury. Promotes adhesion of monocytes. Stimulates proliferation and migration of monocytes/macrophages. Through its action on intimal smooth muscle cells and macrophages, may accelerate intimal thickening and macrophage foam cell formation in the process of atherosclerosis. Regulates hypoxia-enhanced adhesion of hematopoietic stem and progenitor cells to the bone marrow stromal cells via a PLAUR-mediated pathway. This function is mediated by the N-terminal ectodomain. Metabolic regulator, which functions to maintain the adequate balance between lipid storage and oxidation in response to changing environmental conditions, such as temperature and diet. The N-terminal ectodomain negatively regulates adipose tissue energy expenditure, acting through the inhibition the BMP/Smad pathway. May regulate signaling by the heterodimeric neurotrophic cytokine CLCF1-CRLF1 bound to the CNTFR receptor by promoting the endocytosis of the tripartite complex CLCF1-CRLF1-CNTFR and lysosomal degradation. May regulate IL6 signaling, decreasing cis signaling, possibly by interfering with IL6-binding to membrane-bound IL6R, while up-regulating trans signaling via soluble IL6R.
• Tissue Specificity: Highly expressed in brain (at protein level) . Most abundant in the cerebellum, cerebral cortex and occipital pole; low levels in the putamen and thalamus . Expression is significantly reduced in the frontal cortex of patients suffering from Alzheimer disease . Also expressed in spinal cord, spleen, testis, prostate, ovary, thyroid and lymph nodes .
• Reactome Pathway: Amyloid fiber formation (R-HSA-977225)

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute leukaemia	DISDQFDI	Definitive	Biomarker	[1]
Acute lymphocytic leukaemia	DISPX75S	Definitive	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	Definitive	Altered Expression	[1]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Definitive	Altered Expression	[1]
Multiple sclerosis	DISB2WZI	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Amyloidosis	DISHTAI2	Strong	Biomarker	[4]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[5]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[6]
Carotid stenosis	DISZA8D0	Strong	Biomarker	[7]
Cerebrovascular disease	DISAB237	Strong	Genetic Variation	[8]
Cholestasis	DISDJJWE	Strong	Biomarker	[9]
Depression	DIS3XJ69	Strong	Biomarker	[10]
Familial hypercholesterolemia	DISC06IX	Strong	Biomarker	[11]
Huntington disease	DISQPLA4	Strong	Altered Expression	[12]
Hypercholesterolemia, familial, 1	DISU411W	Strong	Biomarker	[11]
Obesity	DIS47Y1K	Strong	Biomarker	[13]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[14]
Plasma cell myeloma	DIS0DFZ0	Strong	Posttranslational Modification	[15]
Pulmonary arterial hypertension	DISP8ZX5	Strong	Biomarker	[16]
Schizophrenia	DISSRV2N	Strong	Biomarker	[5]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[3]
Vascular disease	DISVS67S	Strong	Biomarker	[8]
Arteriosclerosis	DISK5QGC	moderate	Biomarker	[6]
Atherosclerosis	DISMN9J3	moderate	Biomarker	[6]
Atrial fibrillation	DIS15W6U	moderate	Biomarker	[17]
Familial Alzheimer disease	DISE75U4	moderate	Biomarker	[18]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[17]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[19]
Type-1/2 diabetes	DISIUHAP	moderate	Biomarker	[20]
Early-onset autosomal dominant Alzheimer disease	DISFAUJO	Supportive	Autosomal dominant	[21]
High blood pressure	DISY2OHH	Limited	Biomarker	[22]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Sortilin-related receptor (SORL1) affects the response to substance of Topotecan.	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Sortilin-related receptor (SORL1).	[24]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Sortilin-related receptor (SORL1).	[25]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Sortilin-related receptor (SORL1).	[26]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sortilin-related receptor (SORL1).	[27]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sortilin-related receptor (SORL1).	[28]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Sortilin-related receptor (SORL1).	[29]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Sortilin-related receptor (SORL1).	[27]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Sortilin-related receptor (SORL1).	[30]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Sortilin-related receptor (SORL1).	[32]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Sortilin-related receptor (SORL1).	[33]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Sortilin-related receptor (SORL1).	[34]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Sortilin-related receptor (SORL1).	[32]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Sortilin-related receptor (SORL1).	[27]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Sortilin-related receptor (SORL1).	[35]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of Sortilin-related receptor (SORL1).	[27]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of Sortilin-related receptor (SORL1).	[27]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Sortilin-related receptor (SORL1).	[27]
Ibuprofen	DM8VCBE	Approved	Ibuprofen decreases the expression of Sortilin-related receptor (SORL1).	[27]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Sortilin-related receptor (SORL1).	[25]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Sortilin-related receptor (SORL1).	[36]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Sortilin-related receptor (SORL1).	[24]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Sortilin-related receptor (SORL1).	[38]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of Sortilin-related receptor (SORL1).	[39]
Serotonin	DMOFCRY	Investigative	Serotonin increases the expression of Sortilin-related receptor (SORL1).	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Sortilin-related receptor (SORL1).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Sortilin-related receptor (SORL1).	[37]

References

• [1] Circulating soluble LR11/SorLA levels are highly increased and ameliorated by chemotherapy in acute leukemias.Clin Chim Acta. 2012 Oct 9;413(19-20):1542-8. doi: 10.1016/j.cca.2012.06.025. Epub 2012 Jun 29.
• [2] Chipping away at diagnostics for neurodegenerative diseases.Neurobiol Dis. 2009 Aug;35(2):148-56. doi: 10.1016/j.nbd.2009.02.016. Epub 2009 Mar 10.
• [3] SORLA regulates endosomal trafficking and oncogenic fitness of HER2.Nat Commun. 2019 May 28;10(1):2340. doi: 10.1038/s41467-019-10275-0.
• [4] Impact of SORL1 genetic variations on MRI markers in non-demented elders.Oncotarget. 2016 May 31;7(22):31689-98. doi: 10.18632/oncotarget.9300.
• [5] Genome-wide association study of behavioural and psychiatric features in human prion disease.Transl Psychiatry. 2015 Apr 21;5(4):e552. doi: 10.1038/tp.2015.42.
• [6] LR11/SorLA links triglyceride-rich lipoproteins to risk of developing cardiovascular disease in FH patients.Atherosclerosis. 2015 Dec;243(2):429-37. doi: 10.1016/j.atherosclerosis.2015.10.009. Epub 2015 Oct 13.
• [7] Levels of circulating soluble LR11, a regulator of smooth muscle cell migration, are highly associated with atherosclerotic plaques in patients with carotid artery stenosis.Clin Chim Acta. 2019 Mar;490:69-76. doi: 10.1016/j.cca.2018.12.005. Epub 2018 Dec 12.
• [8] Association of distinct variants in SORL1 with cerebrovascular and neurodegenerative changes related to Alzheimer disease.Arch Neurol. 2008 Dec;65(12):1640-8. doi: 10.1001/archneur.65.12.1640.
• [9] Classification of Cholestatic and Necrotic Hepatotoxicants Using Transcriptomics on Human Precision-Cut Liver Slices.Chem Res Toxicol. 2016 Mar 21;29(3):342-51. doi: 10.1021/acs.chemrestox.5b00491. Epub 2016 Mar 9.
• [10] Exploring the sortilin related receptor, SorLA, in depression.J Affect Disord. 2018 May;232:260-267. doi: 10.1016/j.jad.2018.02.050. Epub 2018 Feb 21.
• [11] Soluble LR11 associates with aortic root calcification in asymptomatic treated male patients with familial hypercholesterolemia.Atherosclerosis. 2017 Oct;265:299-304. doi: 10.1016/j.atherosclerosis.2017.06.018. Epub 2017 Jun 9.
• [12] SORLA-mediated trafficking of TrkB enhances the response of neurons to BDNF.PLoS One. 2013 Aug 19;8(8):e72164. doi: 10.1371/journal.pone.0072164. eCollection 2013.
• [13] SORLA facilitates insulin receptor signaling in adipocytes and exacerbates obesity.J Clin Invest. 2016 Jul 1;126(7):2706-20. doi: 10.1172/JCI84708. Epub 2016 Jun 20.
• [14] Alzheimer disease associated variants in SORL1 accelerate dementia development in Parkinson disease.Neurosci Lett. 2018 May 1;674:123-126. doi: 10.1016/j.neulet.2018.03.036. Epub 2018 Mar 19.
• [15] Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse.Oncotarget. 2016 Dec 6;7(49):80664-80679. doi: 10.18632/oncotarget.13025.
• [16] Deletion of LR11 Attenuates Hypoxia-Induced Pulmonary Arterial Smooth Muscle Cell Proliferation With Medial Thickening in Mice.Arterioscler Thromb Vasc Biol. 2016 Sep;36(9):1972-9. doi: 10.1161/ATVBAHA.116.307900. Epub 2016 Aug 4.
• [17] Biobank-driven genomic discovery yields new insight into atrial fibrillation biology.Nat Genet. 2018 Sep;50(9):1234-1239. doi: 10.1038/s41588-018-0171-3. Epub 2018 Jul 30.
• [18] SORL1 Variants in Familial Alzheimer's Disease.J Alzheimers Dis. 2018;61(4):1275-1281. doi: 10.3233/JAD-170590.
• [19] Markedly induced expression of LR11 in atherosclerosis.J Atheroscler Thromb. 2000;7(1):21-5. doi: 10.5551/jat1994.7.21.
• [20] Diabetes-associated SorCS1 regulates Alzheimer's amyloid-beta metabolism: evidence for involvement of SorL1 and the retromer complex.J Neurosci. 2010 Sep 29;30(39):13110-5. doi: 10.1523/JNEUROSCI.3872-10.2010.
• [21] High frequency of potentially pathogenic SORL1 mutations in autosomal dominant early-onset Alzheimer disease. Mol Psychiatry. 2012 Sep;17(9):875-9. doi: 10.1038/mp.2012.15. Epub 2012 Apr 3.
• [22] Genetic risk factors for cerebral small-vessel disease in hypertensive patients from a genetically isolated population.J Neurol Neurosurg Psychiatry. 2011 Jan;82(1):41-4. doi: 10.1136/jnnp.2009.176362. Epub 2010 Jul 28.
• [23] Omega-3 fatty acid docosahexaenoic acid increases SorLA/LR11, a sorting protein with reduced expression in sporadic Alzheimer's disease (AD): relevance to AD prevention.J Neurosci. 2007 Dec 26;27(52):14299-307. doi: 10.1523/JNEUROSCI.3593-07.2007.
• [24] 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.
• [25] 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.
• [26] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [27] 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.
• [28] 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.
• [29] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [30] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [31] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [32] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [33] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [34] 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.
• [35] 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.
• [36] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [37] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [38] 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.
• [39] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.
• [40] Effects of serotonin on expression of the LDL receptor family member LR11 and 7-ketocholesterol-induced apoptosis in human vascular smooth muscle cells. Biochem Biophys Res Commun. 2014 Apr 18;446(4):906-10. doi: 10.1016/j.bbrc.2014.03.031. Epub 2014 Mar 17.
• [41] 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.