Details of Drug Off-Target (DOT)

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

• DOT Name: Transcription factor SOX-7 (SOX7)
• Gene Name: SOX7
• Related Disease:
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
  Acute myelogenous leukaemia
  Acute myocardial infarction
  Advanced cancer
  Bone osteosarcoma
  Childhood myelodysplastic syndrome
  Clear cell renal carcinoma
  Colorectal carcinoma
  Congenital diaphragmatic hernia
  Dilated cardiomyopathy 1A
  Endometrial cancer
  Endometrial carcinoma
  Gastric cancer
  Glioma
  Hepatitis B virus infection
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Lung adenocarcinoma
  Lung carcinoma
  Malignant glioma
  Myelodysplastic syndrome
  Neoplasm
  Osteosarcoma
  Prostate neoplasm
  Renal cell carcinoma
  Stomach cancer
  Adult glioblastoma
  Bladder cancer
  Breast carcinoma
  Carcinoma
  Glioblastoma multiforme
  Pancreatic cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Adenocarcinoma
  Breast cancer
  Colorectal neoplasm
  Lung cancer
  Nasopharyngeal carcinoma
  Non-small-cell lung cancer
  Prostate cancer
  Prostate carcinoma
  Squamous cell carcinoma
  Temporal lobe epilepsy
• UniProt ID: SOX7_HUMAN
• Pfam ID: PF00505 ; PF12067
• Sequence:
  MASLLGAYPWPEGLECPALDAELSDGQSPPAVPRPPGDKGSESRIRRPMNAFMVWAKDER
  KRLAVQNPDLHNAELSKMLGKSWKALTLSQKRPYVDEAERLRLQHMQDYPNYKYRPRRKK
  QAKRLCKRVDPGFLLSSLSRDQNALPEKRSGSRGALGEKEDRGEYSPGTALPSLRGCYHE
  GPAGGGGGGTPSSVDTYPYGLPTPPEMSPLDVLEPEQTFFSSPCQEEHGHPRRIPHLPGH
  PYSPEYAPSPLHCSHPLGSLALGQSPGVSMMSPVPGCPPSPAYYSPATYHPLHSNLQAHL
  GQLSPPPEHPGFDALDQLSQVELLGDMDRNEFDQYLNTPGHPDSATGAMALSGHVPVSQV
  TPTGPTETSLISVLADATATYYNSYSVS
• Function: Binds to and activates the CDH5 promoter, hence plays a role in the transcriptional regulation of genes expressed in the hemogenic endothelium and blocks further differentiation into blood precursors. May be required for the survival of both hematopoietic and endothelial precursors during specification. Competes with GATA4 for binding and activation of the FGF3 promoter. Represses Wnt/beta-catenin-stimulated transcription, probably by targeting CTNNB1 to proteasomal degradation. Binds the DNA sequence 5'-AACAAT-3'.
• Tissue Specificity: Widely expressed in adult and fetal tissues. Present both in mesenchymal and epithelial cells in some adult tissues, including colon. Tends to be down-regulated in prostate adenocarcinomas and colorectal tumors due to promoter hypermethylation.
• Reactome Pathway: Deactivation of the beta-catenin transactivating complex (R-HSA-3769402)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epithelial ovarian cancer	DIS56MH2	Definitive	Altered Expression	[1]
Ovarian cancer	DISZJHAP	Definitive	Altered Expression	[1]
Ovarian neoplasm	DISEAFTY	Definitive	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Acute myocardial infarction	DISE3HTG	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[5]
Childhood myelodysplastic syndrome	DISMN80I	Strong	Biomarker	[6]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Congenital diaphragmatic hernia	DIS0IPVU	Strong	Genetic Variation	[8]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Altered Expression	[9]
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[10]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[10]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[11]
Glioma	DIS5RPEH	Strong	Biomarker	[12]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
leukaemia	DISS7D1V	Strong	Altered Expression	[2]
Leukemia	DISNAKFL	Strong	Altered Expression	[2]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[15]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[16]
Malignant glioma	DISFXKOV	Strong	Biomarker	[17]
Myelodysplastic syndrome	DISYHNUI	Strong	Posttranslational Modification	[18]
Neoplasm	DISZKGEW	Strong	Biomarker	[19]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[5]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[20]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[4]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[11]
Adult glioblastoma	DISVP4LU	moderate	Altered Expression	[21]
Bladder cancer	DISUHNM0	moderate	Biomarker	[22]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[23]
Carcinoma	DISH9F1N	moderate	Altered Expression	[24]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[21]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[24]
Urinary bladder cancer	DISDV4T7	moderate	Biomarker	[22]
Urinary bladder neoplasm	DIS7HACE	moderate	Biomarker	[22]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[25]
Breast cancer	DIS7DPX1	Limited	Biomarker	[23]
Colorectal neoplasm	DISR1UCN	Limited	Altered Expression	[25]
Lung cancer	DISCM4YA	Limited	Altered Expression	[16]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[26]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[27]
Prostate cancer	DISF190Y	Limited	Altered Expression	[20]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[20]
Squamous cell carcinoma	DISQVIFL	Limited	Altered Expression	[28]
Temporal lobe epilepsy	DISNOPXX	Limited	Biomarker	[29]

9 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 Transcription factor SOX-7 (SOX7).	[30]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transcription factor SOX-7 (SOX7).	[31]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription factor SOX-7 (SOX7).	[32]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transcription factor SOX-7 (SOX7).	[33]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transcription factor SOX-7 (SOX7).	[34]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Transcription factor SOX-7 (SOX7).	[35]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Transcription factor SOX-7 (SOX7).	[36]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Transcription factor SOX-7 (SOX7).	[30]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transcription factor SOX-7 (SOX7).	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Transcription factor SOX-7 (SOX7).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Transcription factor SOX-7 (SOX7).	[38]

References

• [1] Reduced expression of SOX7 in ovarian cancer: a novel tumor suppressor through the Wnt/-catenin signaling pathway.J Ovarian Res. 2014 Sep 5;7:87. doi: 10.1186/s13048-014-0087-1.
• [2] Suppression of SOX7 by DNA methylation and its tumor suppressor function in acute myeloid leukemia.Blood. 2015 Jun 18;125(25):3928-36. doi: 10.1182/blood-2014-06-580993. Epub 2015 May 4.
• [3] MiR-128/SOX7 alleviates myocardial ischemia injury by regulating IL-33/sST2 in acute myocardial infarction.Biol Chem. 2019 Mar 26;400(4):533-544. doi: 10.1515/hsz-2018-0207.
• [4] Classic SRY-box protein SOX7 functions as a tumor suppressor regulating WNT signaling and is methylated in renal cell carcinoma.FASEB J. 2019 Jan;33(1):254-263. doi: 10.1096/fj.201701453RR. Epub 2018 Jun 29.
• [5] Overexpression of miR-664 is associated with enhanced osteosarcoma cell migration and invasion ability via targeting SOX7. Clin Exp Med. 2017 Feb;17(1):51-58.
• [6] Methylation of the CpG island near SOX7 gene promoter is correlated with the poor prognosis of patients with myelodysplastic syndrome.Tohoku J Exp Med. 2012 Jun;227(2):119-28. doi: 10.1620/tjem.227.119.
• [7] TGF-1 mediates the effects of aspirin on colonic tumor cell proliferation and apoptosis.Oncol Lett. 2018 Apr;15(4):5903-5909. doi: 10.3892/ol.2018.8047. Epub 2018 Feb 14.
• [8] Mouse model reveals the role of SOX7 in the development of congenital diaphragmatic hernia associated with recurrent deletions of 8p23.1.Hum Mol Genet. 2012 Sep 15;21(18):4115-25. doi: 10.1093/hmg/dds241. Epub 2012 Jun 20.
• [9] Impact of SOX18 expression in cancer cells and vessels on the outcome of invasive ductal breast carcinoma.Cell Oncol (Dordr). 2013 Dec;36(6):469-83. doi: 10.1007/s13402-013-0151-7. Epub 2013 Sep 25.
• [10] Down-regulation of Sox7 is associated with aberrant activation of Wnt/b-catenin signaling in endometrial cancer.Oncotarget. 2012 Dec;3(12):1546-56. doi: 10.18632/oncotarget.667.
• [11] Decreased expression of Sox7 correlates with the upregulation of the Wnt/-catenin signaling pathway and the poor survival of gastric cancer patients.Int J Mol Med. 2014 Jul;34(1):197-204. doi: 10.3892/ijmm.2014.1759. Epub 2014 Apr 25.
• [12] Long noncoding RNA AB073614 promotes the malignance of glioma by activating Wnt/-catenin signaling through downregulating SOX7.Oncotarget. 2017 Jul 17;8(39):65577-65587. doi: 10.18632/oncotarget.19305. eCollection 2017 Sep 12.
• [13] Identification of Slug and SOX7 as transcriptional repressors binding to the hepatitis B virus core promoter.J Hepatol. 2017 Sep 5:S0168-8278(17)32276-6. doi: 10.1016/j.jhep.2017.08.033. Online ahead of print.
• [14] miR-935 Promotes Liver Cancer Cell Proliferation and Migration by Targeting SOX7.Oncol Res. 2017 Mar 13;25(3):427-435. doi: 10.3727/096504016X14747300207374. Epub 2016 Sep 30.
• [15] Decreased expression of SOX7 is correlated with poor prognosis in lung adenocarcinoma patients.Pathol Oncol Res. 2012 Oct;18(4):1039-45. doi: 10.1007/s12253-012-9542-8. Epub 2012 Jul 10.
• [16] SOX7 regulates MAPK/ERK-BIM mediated apoptosis in cancer cells.Oncogene. 2019 Aug;38(34):6196-6210. doi: 10.1038/s41388-019-0865-8. Epub 2019 Jul 22.
• [17] Sox7 promotes high-grade glioma by increasing VEGFR2-mediated vascular abnormality.J Exp Med. 2018 Mar 5;215(3):963-983. doi: 10.1084/jem.20170123. Epub 2018 Feb 14.
• [18] SOX7 methylation is an independent prognostic factor in myelodysplastic syndromes.Pathol Res Pract. 2019 Feb;215(2):322-328. doi: 10.1016/j.prp.2018.12.003. Epub 2018 Dec 6.
• [19] Validation of epigenetic markers to identify colitis associated cancer: Results of module 1 of the ENDCAP-C study.EBioMedicine. 2019 Jan;39:265-271. doi: 10.1016/j.ebiom.2018.11.034. Epub 2018 Nov 22.
• [20] Sox7 negatively regulates prostate-specific membrane antigen (PSMA) expression through PSMA-enhancer.Prostate. 2019 Mar;79(4):370-378. doi: 10.1002/pros.23743. Epub 2018 Nov 28.
• [21] MiR-595 targeting regulation of SOX7 expression promoted cell proliferation of human glioblastoma.Biomed Pharmacother. 2016 May;80:121-126. doi: 10.1016/j.biopha.2016.03.008. Epub 2016 Mar 19.
• [22] MiRNA-616 aggravates the progression of bladder cancer by regulating cell proliferation, migration and apoptosis through downregulating SOX7.Eur Rev Med Pharmacol Sci. 2019 Nov;23(21):9304-9312. doi: 10.26355/eurrev_201911_19423.
• [23] Long noncoding RNA HAND2-AS1 restrains proliferation and metastasis of breast cancer cells through sponging miR-1275 and promoting SOX7.Cancer Biomark. 2020;27(1):85-94. doi: 10.3233/CBM-190530.
• [24] Clinical signicance and prognostic value of SOX7 expression in liver and pancreatic carcinoma.Mol Med Rep. 2017 Jul;16(1):499-506. doi: 10.3892/mmr.2017.6660. Epub 2017 May 31.
• [25] Sox7 Is an independent checkpoint for beta-catenin function in prostate and colon epithelial cells.Mol Cancer Res. 2008 Sep;6(9):1421-30. doi: 10.1158/1541-7786.MCR-07-2175.
• [26] MicroRNA-494-3p Promotes Cell Growth, Migration, and Invasion of Nasopharyngeal Carcinoma by Targeting Sox7.Technol Cancer Res Treat. 2018 Jan 1;17:1533033818809993. doi: 10.1177/1533033818809993.
• [27] Knockdown of miR?35 increases paclitaxel sensitivity via regulation of SOX7 in nonsmallcell lung cancer.Mol Med Rep. 2018 Sep;18(3):3397-3402. doi: 10.3892/mmr.2018.9330. Epub 2018 Jul 27.
• [28] Decreased expression of SOX7 induces cell proliferation and invasion and correlates with poor prognosis in oral squamous cell carcinoma.J Oral Pathol Med. 2017 Oct;46(9):752-758. doi: 10.1111/jop.12566. Epub 2017 Mar 28.
• [29] LncRNA FTX inhibits hippocampal neuron apoptosis by regulating miR-21-5p/SOX7 axis in a rat model of temporal lobe epilepsy.Biochem Biophys Res Commun. 2019 Apr 23;512(1):79-86. doi: 10.1016/j.bbrc.2019.03.019. Epub 2019 Mar 11.
• [30] 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.
• [31] Constitutive gene expression predisposes morphogen-mediated cell fate responses of NT2/D1 and 27X-1 human embryonal carcinoma cells. Stem Cells. 2007 Mar;25(3):771-8. doi: 10.1634/stemcells.2006-0271. Epub 2006 Nov 30.
• [32] 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.
• [33] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [34] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [35] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [36] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [37] 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.
• [38] 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.
• [39] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.