Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVI1RAR)

• DOT Name: Transcription factor SOX-1 (SOX1)
• Gene Name: SOX1
• Related Disease:
  LambertEaton myasthenic syndrome
  Adult glioblastoma
  Advanced cancer
  Benign neoplasm
  Bladder cancer
  Cervical cancer
  Cervical carcinoma
  Classic Hodgkin lymphoma
  Endometrial carcinoma
  Esophageal squamous cell carcinoma
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Isolated neonatal sclerosing cholangitis
  Liver cirrhosis
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Polyneuropathy
  Prostate cancer
  Severe combined immunodeficiency
  Small-cell lung cancer
  Squamous cell carcinoma
  Stomach cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Uterine cervix neoplasm
  Laryngeal squamous cell carcinoma
  Nasopharyngeal carcinoma
  Adult hepatocellular carcinoma
  Epithelial ovarian cancer
  Liver cancer
  Ovarian cancer
  Ovarian neoplasm
• UniProt ID: SOX1_HUMAN
• Pfam ID: PF00505 ; PF12336
• Sequence:
  MYSMMMETDLHSPGGAQAPTNLSGPAGAGGGGGGGGGGGGGGGAKANQDRVKRPMNAFMV
  WSRGQRRKMAQENPKMHNSEISKRLGAEWKVMSEAEKRPFIDEAKRLRALHMKEHPDYKY
  RPRRKTKTLLKKDKYSLAGGLLAAGAGGGGAAVAMGVGVGVGAAAVGQRLESPGGAAGGG
  YAHVNGWANGAYPGSVAAAAAAAAMMQEAQLAYGQHPGAGGAHPHAHPAHPHPHHPHAHP
  HNPQPMHRYDMGALQYSPISNSQGYMSASPSGYGGLPYGAAAAAAAAAGGAHQNSAVAAA
  AAAAAASSGALGALGSLVKSEPSGSPPAPAHSRAPCPGDLREMISMYLPAGEGGDPAAAA
  AAAAQSRLHSLPQHYQGAGAGVNGTVPLTHI
• Function: Transcriptional activator. May function as a switch in neuronal development. Keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differentiation.
• Tissue Specificity: Mainly expressed in the developing central nervous system.
• Reactome Pathway:
  Formation of the posterior neural plate (R-HSA-9832991)
  Formation of the anterior neural plate (R-HSA-9823739)

Molecular Interaction Atlas (MIA) of This DOT

36 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
LambertEaton myasthenic syndrome	DISN0Q7Q	Definitive	Biomarker	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Benign neoplasm	DISDUXAD	Strong	Genetic Variation	[4]
Bladder cancer	DISUHNM0	Strong	Posttranslational Modification	[5]
Cervical cancer	DISFSHPF	Strong	Biomarker	[6]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[6]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[7]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[8]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[3]
Gastric cancer	DISXGOUK	Strong	Biomarker	[9]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[10]
Isolated neonatal sclerosing cholangitis	DIS6G5UY	Strong	Altered Expression	[11]
Liver cirrhosis	DIS4G1GX	Strong	Altered Expression	[10]
Lung cancer	DISCM4YA	Strong	Posttranslational Modification	[12]
Lung carcinoma	DISTR26C	Strong	Posttranslational Modification	[12]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[12]
Polyneuropathy	DISB9G3W	Strong	Biomarker	[13]
Prostate cancer	DISF190Y	Strong	Altered Expression	[14]
Severe combined immunodeficiency	DIS6MF4Q	Strong	Biomarker	[15]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[13]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[16]
Stomach cancer	DISKIJSX	Strong	Biomarker	[9]
Urinary bladder cancer	DISDV4T7	Strong	Posttranslational Modification	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Posttranslational Modification	[5]
Uterine cervix neoplasm	DIS0BYVV	Strong	Biomarker	[16]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Biomarker	[17]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Posttranslational Modification	[18]
Adult hepatocellular carcinoma	DIS6ZPAI	Limited	Posttranslational Modification	[19]
Epithelial ovarian cancer	DIS56MH2	Limited	Posttranslational Modification	[19]
Liver cancer	DISDE4BI	Limited	Posttranslational Modification	[19]
Ovarian cancer	DISZJHAP	Limited	Posttranslational Modification	[19]
Ovarian neoplasm	DISEAFTY	Limited	Posttranslational Modification	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Transcription factor SOX-1 (SOX1).	[20]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Transcription factor SOX-1 (SOX1).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Transcription factor SOX-1 (SOX1).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription factor SOX-1 (SOX1).	[21]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transcription factor SOX-1 (SOX1).	[22]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Transcription factor SOX-1 (SOX1).	[24]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Transcription factor SOX-1 (SOX1).	[25]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Transcription factor SOX-1 (SOX1).	[26]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Transcription factor SOX-1 (SOX1).	[27]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Transcription factor SOX-1 (SOX1).	[28]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Transcription factor SOX-1 (SOX1).	[25]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Transcription factor SOX-1 (SOX1).	[29]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Transcription factor SOX-1 (SOX1).	[31]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Transcription factor SOX-1 (SOX1).	[32]

References

• [1] SOX1 antibodies are markers of paraneoplastic Lambert-Eaton myasthenic syndrome.Neurology. 2008 Mar 18;70(12):924-8. doi: 10.1212/01.wnl.0000281663.81079.24. Epub 2007 Nov 21.
• [2] Oncogenic activity of SOX1 in glioblastoma.Sci Rep. 2017 Apr 20;7:46575. doi: 10.1038/srep46575.
• [3] Aberrant DNA methylation of PAX1, SOX1 and ZNF582 genes as potential biomarkers for esophageal squamous cell carcinoma.Biomed Pharmacother. 2019 Dec;120:109488. doi: 10.1016/j.biopha.2019.109488. Epub 2019 Oct 16.
• [4] An epigenetic marker panel for screening and prognostic prediction of ovarian cancer.Int J Cancer. 2009 Jan 15;124(2):387-93. doi: 10.1002/ijc.23957.
• [5] A DNA hypermethylation profile reveals new potential biomarkers for the evaluation of prognosis in urothelial bladder cancer.APMIS. 2017 Sep;125(9):787-796. doi: 10.1111/apm.12719. Epub 2017 Jun 6.
• [6] Genome-wide methylome analysis using MethylCap-seq uncovers 4 hypermethylated markers with high sensitivity for both adeno- and squamous-cell cervical carcinoma.Oncotarget. 2016 Dec 6;7(49):80735-80750. doi: 10.18632/oncotarget.12598.
• [7] Paraneoplastic limbic encephalitis with SOX1 and PCA2 antibodies and relapsing neurological symptoms in an adolescent with Hodgkin lymphoma.Eur J Paediatr Neurol. 2017 Jul;21(4):661-665. doi: 10.1016/j.ejpn.2017.03.005. Epub 2017 Mar 27.
• [8] DNA methylation as a biomarker for the detection of hidden carcinoma in endometrial atypical hyperplasia.Gynecol Oncol. 2014 Dec;135(3):552-9. doi: 10.1016/j.ygyno.2014.10.018. Epub 2014 Oct 23.
• [9] Identifying novel biomarkers of gastric cancer through integration analysis of single nucleotide polymorphisms and gene expression profile.Int J Biol Markers. 2015 Jul 22;30(3):e321-6. doi: 10.5301/jbm.5000145.
• [10] Methylation of SOX1 and VIM promoters in serum as potential biomarkers for hepatocellular carcinoma.Neoplasma. 2017;64(5):745-753. doi: 10.4149/neo_2017_513.
• [11] Generation of highly purified neural stem cells from human adipose-derived mesenchymal stem cells by Sox1 activation.Stem Cells Dev. 2014 Mar 1;23(5):515-29. doi: 10.1089/scd.2013.0263. Epub 2014 Jan 20.
• [12] Epigenetic inactivation of SOX1 promotes cell migration in lung cancer.Tumour Biol. 2015 Jun;36(6):4603-10. doi: 10.1007/s13277-015-3107-x. Epub 2015 Jan 23.
• [13] Caveats and Pitfalls of SOX1 Autoantibody Testing With a Commercial Line Blot Assay in Paraneoplastic Neurological Investigations.Front Immunol. 2019 Apr 12;10:769. doi: 10.3389/fimmu.2019.00769. eCollection 2019.
• [14] Epigenetic regulation of CpG promoter methylation in invasive prostate cancer cells.Mol Cancer. 2010 Oct 7;9:267. doi: 10.1186/1476-4598-9-267.
• [15] SOX1 suppresses cell growth and invasion in cervical cancer.Gynecol Oncol. 2013 Oct;131(1):174-81. doi: 10.1016/j.ygyno.2013.07.111. Epub 2013 Aug 6.
• [16] Concordance analysis of methylation biomarkers detection in self-collected and physician-collected samples in cervical neoplasm.BMC Cancer. 2015 May 19;15:418. doi: 10.1186/s12885-015-1411-x.
• [17] SOX 1, contrary to SOX 2, suppresses proliferation, migration, and invasion in human laryngeal squamous cell carcinoma by inhibiting the Wnt/-catenin pathway.Tumour Biol. 2015 Nov;36(11):8625-35. doi: 10.1007/s13277-015-3389-z. Epub 2015 Jun 4.
• [18] SOX1 down-regulates -catenin and reverses malignant phenotype in nasopharyngeal carcinoma.Mol Cancer. 2014 Nov 26;13:257. doi: 10.1186/1476-4598-13-257.
• [19] Cisplatin-induced downregulation of SOX1 increases drug resistance by activating autophagy in non-small cell lung cancer cell.Biochem Biophys Res Commun. 2013 Sep 20;439(2):187-90. doi: 10.1016/j.bbrc.2013.08.065. Epub 2013 Aug 29.
• [20] 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.
• [21] 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.
• [22] Bisphenol A Represses Dopaminergic Neuron Differentiation from Human Embryonic Stem Cells through Downregulating the Expression of Insulin-like Growth Factor 1. Mol Neurobiol. 2017 Jul;54(5):3798-3812. doi: 10.1007/s12035-016-9898-y. Epub 2016 Jun 7.
• [23] Association of Arsenic Exposure with Whole Blood DNA Methylation: An Epigenome-Wide Study of Bangladeshi Adults. Environ Health Perspect. 2019 May;127(5):57011. doi: 10.1289/EHP3849. Epub 2019 May 28.
• [24] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [25] 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.
• [26] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [27] Neuronal and cardiac toxicity of pharmacological compounds identified through transcriptomic analysis of human pluripotent stem cell-derived embryoid bodies. Toxicol Appl Pharmacol. 2021 Dec 15;433:115792. doi: 10.1016/j.taap.2021.115792. Epub 2021 Nov 3.
• [28] Effects of all-trans and 9-cis retinoic acid on differentiating human neural stem cells in vitro. Toxicology. 2023 Mar 15;487:153461. doi: 10.1016/j.tox.2023.153461. Epub 2023 Feb 16.
• [29] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [30] 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.
• [31] 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.
• [32] Characterization of paraquat-induced miRNA profiling response in hNPCs undergoing proliferation. Int J Mol Sci. 2014 Oct 13;15(10):18422-36. doi: 10.3390/ijms151018422.