Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNT50CC)

• DOT Name: Transcription factor SOX-21 (SOX21)
• Synonyms: SOX-A
• Gene Name: SOX21
• Related Disease:
  Glioma
  Advanced cancer
  Campomelic dysplasia
  Lung adenocarcinoma
  Neoplasm
  Obstructive sleep apnea
  Pituitary gland disorder
  Small-cell lung cancer
  Liposarcoma
  Fibrosarcoma
• UniProt ID: SOX21_HUMAN
• Pfam ID: PF00505 ; PF12336
• Sequence:
  MSKPVDHVKRPMNAFMVWSRAQRRKMAQENPKMHNSEISKRLGAEWKLLTESEKRPFIDE
  AKRLRAMHMKEHPDYKYRPRRKPKTLLKKDKFAFPVPYGLGGVADAEHPALKAGAGLHAG
  AGGGLVPESLLANPEKAAAAAAAAAARVFFPQSAAAAAAAAAAAAAGSPYSLLDLGSKMA
  EISSSSSGLPYASSLGYPTAGAGAFHGAAAAAAAAAAAAGGHTHSHPSPGNPGYMIPCNC
  SAWPSPGLQPPLAYILLPGMGKPQLDPYPAAYAAAL
• Function: May play a role as an activator of transcription of OPRM1. Overexpression of SOX21 can up-regulate the OPRM1 distal promoter activity in mor-expressing neuronal cells. May play a role in ameloblast differentiation.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Campomelic dysplasia	DISVTW53	Strong	Biomarker	[3]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Obstructive sleep apnea	DIS0SVD1	Strong	Biomarker	[5]
Pituitary gland disorder	DIS7XB48	Strong	Genetic Variation	[6]
Small-cell lung cancer	DISK3LZD	Strong	Altered Expression	[7]
Liposarcoma	DIS8IZVM	moderate	Biomarker	[8]
Fibrosarcoma	DISWX7MU	Limited	Altered Expression	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Transcription factor SOX-21 (SOX21).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Transcription factor SOX-21 (SOX21).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Transcription factor SOX-21 (SOX21).	[11]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Transcription factor SOX-21 (SOX21).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Transcription factor SOX-21 (SOX21).	[9]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Transcription factor SOX-21 (SOX21).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transcription factor SOX-21 (SOX21).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transcription factor SOX-21 (SOX21).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transcription factor SOX-21 (SOX21).	[16]

References

• [1] Forced expression of Sox21 inhibits Sox2 and induces apoptosis in human glioma cells.Int J Cancer. 2011 Jul 1;129(1):45-60. doi: 10.1002/ijc.25647. Epub 2010 Nov 9.
• [2] SOX21-AS1 is associated with clinical stage and regulates cell proliferation in nephroblastoma.Biosci Rep. 2019 May 17;39(5):BSR20190602. doi: 10.1042/BSR20190602. Print 2019 May 31.
• [3] Isolation of a novel Sry-related gene that is expressed in high-metastatic K-1735 murine melanoma cells.Genomics. 1997 Jan 1;39(1):30-7. doi: 10.1006/geno.1996.4483.
• [4] A Novel Long Non-Coding RNA, SOX21-AS1, Indicates a Poor Prognosis and Promotes Lung Adenocarcinoma Proliferation.Cell Physiol Biochem. 2017;42(5):1857-1869. doi: 10.1159/000479543. Epub 2017 Jul 27.
• [5] Effect of Supplemental Oxygen on Blood Pressure in Obstructive Sleep Apnea (SOX). A Randomized Continuous Positive Airway Pressure Withdrawal Trial.Am J Respir Crit Care Med. 2019 Jan 15;199(2):211-219. doi: 10.1164/rccm.201802-0240OC.
• [6] Sox21 deletion in mice causes postnatal growth deficiency without physiological disruption of hypothalamic-pituitary endocrine axes.Mol Cell Endocrinol. 2017 Jan 5;439:213-223. doi: 10.1016/j.mce.2016.09.005. Epub 2016 Sep 8.
• [7] Serological identification of embryonic neural proteins as highly immunogenic tumor antigens in small cell lung cancer.Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4198-203. doi: 10.1073/pnas.97.8.4198.
• [8] The Roles of Sox Family Genes in Sarcoma.Curr Drug Targets. 2016;17(15):1761-1772. doi: 10.2174/1389450117666160502145311.
• [9] 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.
• [10] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [11] 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.
• [12] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [13] 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.
• [14] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [15] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [16] Transcriptomic?pathway?and?benchmark dose analysis of Bisphenol A, Bisphenol S, Bisphenol F, and 3,3',5,5'-Tetrabromobisphenol A in H9 human embryonic stem cells. Toxicol In Vitro. 2021 Apr;72:105097. doi: 10.1016/j.tiv.2021.105097. Epub 2021 Jan 18.