Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTB37I1)

• DOT Name: Protein SOX-15 (SOX15)
• Synonyms: Protein SOX-12; Protein SOX-20
• Gene Name: SOX15
• Related Disease:
  Esophageal cancer
  Advanced cancer
  Colorectal carcinoma
  Endometriosis
  Esophageal squamous cell carcinoma
  Neoplasm
  Pancreatic cancer
  Pancreatic tumour
  Polycystic ovarian syndrome
  Prostate cancer
  Prostate carcinoma
  Thyroid gland carcinoma
  Atrial fibrillation
  Familial atrial fibrillation
  Lung cancer
  Lung carcinoma
• UniProt ID: SOX15_HUMAN
• Pfam ID: PF00505
• Sequence:
  MALPGSSQDQAWSLEPPAATAAASSSSGPQEREGAGSPAAPGTLPLEKVKRPMNAFMVWS
  SAQRRQMAQQNPKMHNSEISKRLGAQWKLLDEDEKRPFVEEAKRLRARHLRDYPDYKYRP
  RRKAKSSGAGPSRCGQGRGNLASGGPLWGPGYATTQPSRGFGYRPPSYSTAYLPGSYGSS
  HCKLEAPSPCSLPQSDPRLQGELLPTYTHYLPPGSPTPYNPPLAGAPMPLTHL
• Function: Transcription factor that binds to DNA at the 5'-AACAATG-3' consensus sequence. Acts as a transcriptional activator and repressor. Binds synergistically with POU5F1 (OCT3/4) to gene promoters. Binds to the FOXK1 promoter and recruits FHL3, resulting in transcriptional activation of FOXK1 which leads to myoblast proliferation. Acts as an inhibitor of myoblast differentiation via transcriptional repression which leads to down-regulation of the muscle-specific genes MYOD and MYOG. Involved in trophoblast giant cell differentiation via enhancement of HAND1 transcriptional activity. Regulates transcription of HRC via binding to it proximal enhancer region. Involved in skeletal muscle regeneration. Also plays a role in the development of myogenic precursor cells.
• Tissue Specificity: Widely expressed in fetal and adult tissues examined, highest level found in fetal spinal cord and adult brain and testis.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal cancer	DISGB2VN	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Endometriosis	DISX1AG8	Strong	Biomarker	[3]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Pancreatic cancer	DISJC981	Strong	Biomarker	[6]
Pancreatic tumour	DIS3U0LK	Strong	Posttranslational Modification	[6]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[7]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[8]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[8]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[5]
Atrial fibrillation	DIS15W6U	moderate	Biomarker	[9]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[9]
Lung cancer	DISCM4YA	moderate	Biomarker	[10]
Lung carcinoma	DISTR26C	moderate	Biomarker	[10]

2 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 Protein SOX-15 (SOX15).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein SOX-15 (SOX15).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein SOX-15 (SOX15).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein SOX-15 (SOX15).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein SOX-15 (SOX15).	[14]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Protein SOX-15 (SOX15).	[15]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Protein SOX-15 (SOX15).	[17]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Protein SOX-15 (SOX15).	[18]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Protein SOX-15 (SOX15).	[19]

References

• [1] The cross-regulation between SOX15 and Wnt signaling pathway.J Cell Physiol. 2017 Dec;232(12):3221-3225. doi: 10.1002/jcp.25802. Epub 2017 Mar 27.
• [2] Effects of SOX15 on the colorectal cancer cells via downregulation of the Wnt/-catenin signaling pathway.Future Oncol. 2018 Aug;14(19):1921-1932. doi: 10.2217/fon-2017-0688. Epub 2018 Jul 18.
• [3] Enhanced expression of the stemness-related factors OCT4, SOX15 and TWIST1 in ectopic endometrium of endometriosis patients.Reprod Biol Endocrinol. 2016 Nov 24;14(1):81. doi: 10.1186/s12958-016-0215-4.
• [4] Inhibition of SOX15 Sensitizes Esophageal Squamous Carcinoma Cells to Paclitaxel.Curr Mol Med. 2019;19(5):349-356. doi: 10.2174/1566524019666190405121139.
• [5] Downregulation of microR-147b represses the proliferation and invasion of thyroid carcinoma cells by inhibiting Wnt/-catenin signaling via targeting SOX15.Mol Cell Endocrinol. 2020 Feb 5;501:110662. doi: 10.1016/j.mce.2019.110662. Epub 2019 Nov 21.
• [6] SOX15 is a candidate tumor suppressor in pancreatic cancer with a potential role in Wnt/-catenin signaling.Oncogene. 2014 Jan 16;33(3):279-88. doi: 10.1038/onc.2012.595. Epub 2013 Jan 14.
• [7] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [8] PseudoFuN: Deriving functional potentials of pseudogenes from integrative relationships with genes and microRNAs across 32 cancers.Gigascience. 2019 May 1;8(5):giz046. doi: 10.1093/gigascience/giz046.
• [9] 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.
• [10] Diverse Targets of -Catenin during the Epithelial-Mesenchymal Transition Define Cancer Stem Cells and Predict Disease Relapse.Cancer Res. 2015 Aug 15;75(16):3398-410. doi: 10.1158/0008-5472.CAN-14-3265. Epub 2015 Jun 29.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [16] 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.
• [17] 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.
• [18] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [19] Comparison of the global gene expression profiles produced by methylparaben, n-butylparaben and 17beta-oestradiol in MCF7 human breast cancer cells. J Appl Toxicol. 2007 Jan-Feb;27(1):67-77. doi: 10.1002/jat.1200.