Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4LG7LA)

• DOT Name: Transcription factor SOX-11 (SOX11)
• Gene Name: SOX11
• Related Disease:
  B-cell lymphoma
  Epithelial ovarian cancer
  Intellectual disability, autosomal dominant 27
  Adenocarcinoma
  Advanced cancer
  Astrocytoma
  B-cell neoplasm
  Benign prostatic hyperplasia
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Burkitt lymphoma
  Carcinoma
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Intellectual disability
  Isolated Pierre-Robin syndrome
  Leukemia
  Malignant glioma
  Medulloblastoma
  Neuroendocrine cancer
  Osteoarthritis
  Ovarian cancer
  Ovarian neoplasm
  Plasma cell myeloma
  Prostate cancer
  Prostate carcinoma
  Small lymphocytic lymphoma
  Small-cell lung cancer
  Thyroid gland papillary carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Head and neck cancer
  Head and neck carcinoma
  Isolated congenital microcephaly
  Melanoma
  Coffin-Siris syndrome
  Adult glioblastoma
  Cleft palate
  Gastric cancer
  Haematological malignancy
  Hereditary leiomyomatosis and renal cell cancer
  Isolated cleft palate
  Mast cell leukaemia
  Stomach cancer
• UniProt ID: SOX11_HUMAN
• PDB ID: 6T78; 6T7A; 6T7C; 6T7D
• Pfam ID: PF00505
• Sequence:
  MVQQAESLEAESNLPREALDTEEGEFMACSPVALDESDPDWCKTASGHIKRPMNAFMVWS
  KIERRKIMEQSPDMHNAEISKRLGKRWKMLKDSEKIPFIREAERLRLKHMADYPDYKYRP
  RKKPKMDPSAKPSASQSPEKSAAGGGGGSAGGGAGGAKTSKGSSKKCGKLKAPAAAGAKA
  GAGKAAQSGDYGGAGDDYVLGSLRVSGSGGGGAGKTVKCVFLDEDDDDDDDDDELQLQIK
  QEPDEEDEEPPHQQLLQPPGQQPSQLLRRYNVAKVPASPTLSSSAESPEGASLYDEVRAG
  ATSGAGGGSRLYYSFKNITKQHPPPLAQPALSPASSRSVSTSSSSSSGSSSGSSGEDADD
  LMFDLSLNFSQSAHSASEQQLGGGAAAGNLSLSLVDKDLDSFSEGSLGSHFEFPDYCTPE
  LSEMIAGDWLEANFSDLVFTY
• Function: Transcription factor that acts as a transcriptional activator. Binds cooperatively with POU3F2/BRN2 or POU3F1/OCT6 to gene promoters, which enhances transcriptional activation. Acts as a transcriptional activator of TEAD2 by binding to its gene promoter and first intron. Plays a redundant role with SOX4 and SOX12 in cell survival of developing tissues such as the neural tube, branchial arches and somites, thereby contributing to organogenesis.
• Tissue Specificity: Expressed primarily in the brain and heart, with low expression in the kidney, pancreas and muscle.

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell lymphoma	DISIH1YQ	Definitive	Biomarker	[1]
Epithelial ovarian cancer	DIS56MH2	Definitive	Altered Expression	[2]
Intellectual disability, autosomal dominant 27	DISLV6WV	Definitive	Autosomal dominant	[3]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[4]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[5]
Astrocytoma	DISL3V18	Strong	Altered Expression	[4]
B-cell neoplasm	DISVY326	Strong	Biomarker	[1]
Benign prostatic hyperplasia	DISI3CW2	Strong	Posttranslational Modification	[6]
Bladder cancer	DISUHNM0	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Burkitt lymphoma	DIS9D5XU	Strong	Altered Expression	[9]
Carcinoma	DISH9F1N	Strong	Altered Expression	[4]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[11]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[12]
Isolated Pierre-Robin syndrome	DISVEHG7	Strong	Genetic Variation	[13]
Leukemia	DISNAKFL	Strong	Altered Expression	[14]
Malignant glioma	DISFXKOV	Strong	Genetic Variation	[15]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[16]
Neuroendocrine cancer	DISVGJET	Strong	Altered Expression	[4]
Osteoarthritis	DIS05URM	Strong	Biomarker	[17]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[2]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[2]
Plasma cell myeloma	DIS0DFZ0	Strong	Genetic Variation	[14]
Prostate cancer	DISF190Y	Strong	Posttranslational Modification	[6]
Prostate carcinoma	DISMJPLE	Strong	Posttranslational Modification	[6]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[18]
Small-cell lung cancer	DISK3LZD	Strong	Altered Expression	[19]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Genetic Variation	[20]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[7]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[7]
Head and neck cancer	DISBPSQZ	moderate	Biomarker	[21]
Head and neck carcinoma	DISOU1DS	moderate	Biomarker	[21]
Isolated congenital microcephaly	DISUXHZ6	moderate	Genetic Variation	[22]
Melanoma	DIS1RRCY	moderate	Biomarker	[23]
Coffin-Siris syndrome	DIS8L03H	Supportive	Autosomal dominant	[24]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[10]
Cleft palate	DIS6G5TF	Limited	Genetic Variation	[25]
Gastric cancer	DISXGOUK	Limited	Biomarker	[26]
Haematological malignancy	DISCDP7W	Limited	Biomarker	[26]
Hereditary leiomyomatosis and renal cell cancer	DISN22G2	Limited	Altered Expression	[27]
Isolated cleft palate	DISV80CD	Limited	Genetic Variation	[25]
Mast cell leukaemia	DIS7VQW9	Limited	Altered Expression	[27]
Stomach cancer	DISKIJSX	Limited	Biomarker	[26]

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-11 (SOX11).	[28]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin increases the methylation of Transcription factor SOX-11 (SOX11).	[35]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transcription factor SOX-11 (SOX11).	[36]

10 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-11 (SOX11).	[29]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Transcription factor SOX-11 (SOX11).	[30]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Transcription factor SOX-11 (SOX11).	[31]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Transcription factor SOX-11 (SOX11).	[29]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Transcription factor SOX-11 (SOX11).	[32]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Transcription factor SOX-11 (SOX11).	[33]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Transcription factor SOX-11 (SOX11).	[34]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Transcription factor SOX-11 (SOX11).	[33]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Transcription factor SOX-11 (SOX11).	[37]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Transcription factor SOX-11 (SOX11).	[38]

References

• [1] Identification of CD5/Cyclin D1 Double-negative Pleomorphic Mantle Cell Lymphoma: A Clinicopathologic, Genetic, and Gene Expression Study.Am J Surg Pathol. 2020 Feb;44(2):232-240. doi: 10.1097/PAS.0000000000001390.
• [2] MicroRNA-223-3p Regulates Ovarian Cancer Cell Proliferation and Invasion by Targeting SOX11 Expression.Int J Mol Sci. 2017 Jun 6;18(6):1208. doi: 10.3390/ijms18061208.
• [3] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [4] SOX11: a potentially useful marker in surgical pathology: a systematic analysis of SOX11 expression in epithelial and non-epithelial tumours.Histopathology. 2019 Feb;74(3):391-405. doi: 10.1111/his.13757. Epub 2018 Dec 2.
• [5] Diagnostic accuracy of SOX11 immunohistochemistry in mantle cell lymphoma: Ameta-analysis.PLoS One. 2019 Nov 12;14(11):e0225096. doi: 10.1371/journal.pone.0225096. eCollection 2019.
• [6] Promoter hypermethylation of SOX11 correlates with adverse clinicopathological features of human prostate cancer.Int J Exp Pathol. 2017 Dec;98(6):341-346. doi: 10.1111/iep.12257. Epub 2018 Jan 8.
• [7] Circular RNA CEP128 acts as a sponge of miR-145-5p in promoting the bladder cancer progression via regulating SOX11.Mol Med. 2018 Jul 31;24(1):40. doi: 10.1186/s10020-018-0039-0.
• [8] Clinical and prognostic significance of SOX11 in breast cancer.Asian Pac J Cancer Prev. 2014;15(13):5483-6. doi: 10.7314/apjcp.2014.15.13.5483.
• [9] Clinicopathological features of aggressive B-cell lymphomas including B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell and Burkitt lymphomas: a study of 44 patients from Argentina.Ann Diagn Pathol. 2013 Jun;17(3):250-5. doi: 10.1016/j.anndiagpath.2012.11.001. Epub 2012 Dec 14.
• [10] Establishing cut-off points with clinical relevance for bcl-2, cyclin D1, p16, p21, p27, p53, Sox11 and WT1 expression in glioblastoma - a short report.Cell Oncol (Dordr). 2018 Apr;41(2):213-221. doi: 10.1007/s13402-017-0362-4. Epub 2017 Dec 7.
• [11] SOX11 regulates apoptosis and cell cycle in hepatocellular carcinoma via Wnt/-catenin signaling pathway.Biotechnol Appl Biochem. 2019 Mar;66(2):240-246. doi: 10.1002/bab.1718. Epub 2018 Dec 17.
• [12] De Novo SOX4 Variants Cause a Neurodevelopmental Disease Associated with Mild Dysmorphism. Am J Hum Genet. 2019 Feb 7;104(2):246-259. doi: 10.1016/j.ajhg.2018.12.014. Epub 2019 Jan 17.
• [13] Ablation of the Sox11 Gene Results in Clefting of the Secondary Palate Resembling the Pierre Robin Sequence.J Biol Chem. 2016 Mar 25;291(13):7107-18. doi: 10.1074/jbc.M115.690875. Epub 2016 Jan 29.
• [14] Nuclear expression of sox11 is highly associated with mantle cell lymphoma but is independent of t(11;14)(q13;q32) in non-mantle cell B-cell neoplasms.Mod Pathol. 2010 Jan;23(1):105-12. doi: 10.1038/modpathol.2009.140. Epub 2009 Oct 2.
• [15] Sox11 expression in astrocytic gliomas: correlation with nestin/c-Met/IDH1-R132H expression phenotypes, p-Stat-3 and survival.Br J Cancer. 2013 May 28;108(10):2142-52. doi: 10.1038/bjc.2013.176. Epub 2013 Apr 25.
• [16] Differential expression and prognostic significance of SOX genes in pediatric medulloblastoma and ependymoma identified by microarray analysis.Neuro Oncol. 2008 Oct;10(5):648-60. doi: 10.1215/15228517-2008-032. Epub 2008 Jun 24.
• [17] Sox4 is involved in osteoarthritic cartilage deterioration through induction of ADAMTS4 and ADAMTS5.FASEB J. 2019 Jan;33(1):619-630. doi: 10.1096/fj.201800259R. Epub 2018 Jul 17.
• [18] Flow cytometric analysis of SOX11: a new diagnostic method for distinguishing B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma from mantle cell lymphoma.Leuk Lymphoma. 2015 May;56(5):1425-31. doi: 10.3109/10428194.2014.953147. Epub 2014 Oct 7.
• [19] SOX4, SOX11 and PAX6 mRNA expression was identified as a (prognostic) marker for the aggressiveness of neuroendocrine tumors of the lung by using next-generation expression analysis (NanoString).Future Oncol. 2015;11(7):1027-36. doi: 10.2217/fon.15.18.
• [20] SOX11 expression in a case of papillary thyroid carcinoma with fibromatosis/fasciitis-like stroma containing BRAF c.1799_1801delTGA and CTNNB1 c.133T>C mutations.Virchows Arch. 2019 Oct;475(4):519-525. doi: 10.1007/s00428-019-02619-4. Epub 2019 Jul 20.
• [21] Sox11 promotes head and neck cancer progression via the regulation of SDCCAG8.J Exp Clin Cancer Res. 2019 Mar 29;38(1):138. doi: 10.1186/s13046-019-1146-7.
• [22] Deletions and de novo mutations of SOX11 are associated with a neurodevelopmental disorder with features of Coffin-Siris syndrome. J Med Genet. 2016 Mar;53(3):152-62. doi: 10.1136/jmedgenet-2015-103393. Epub 2015 Nov 5.
• [23] Increased expression of sex determining region Y-box 11 (SOX11) in cutaneous malignant melanoma.J Int Med Res. 2013 Aug;41(4):1221-7. doi: 10.1177/0300060513476592. Epub 2013 Jul 18.
• [24] De novo SOX11 mutations cause Coffin-Siris syndrome. Nat Commun. 2014 Jun 2;5:4011. doi: 10.1038/ncomms5011.
• [25] Observation of Cleft Palate in an Individual with SOX11 Mutation: Indication of a Role for SOX11 in Human Palatogenesis.Cleft Palate Craniofac J. 2018 Mar;55(3):456-461. doi: 10.1177/1055665617739312. Epub 2017 Dec 14.
• [26] Serum SOX11 promoter methylation is a novel biomarker for the diagnosis of Hepatitis B virus-related hepatocellular carcinoma.Neoplasma. 2016;63(3):419-26. doi: 10.4149/311_151029N552.
• [27] SOX11 expression as a MRD molecular marker for MCL in comparison with t(11;14) and IGH rearrangement.Med Oncol. 2018 Mar 8;35(4):49. doi: 10.1007/s12032-018-1111-x.
• [28] 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.
• [29] 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.
• [30] 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.
• [31] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [32] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [33] 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.
• [34] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [35] Reduced camptothecin sensitivity of estrogen receptor-positive human breast cancer cells following exposure to di(2-ethylhexyl)phthalate (DEHP) is associated with DNA methylation changes. Environ Toxicol. 2019 Apr;34(4):401-414.
• [36] 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.
• [37] 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.
• [38] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.