Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT93P8C9)

• DOT Name: Transcription factor SOX-12 (SOX12)
• Synonyms: Protein SOX-22
• Gene Name: SOX12
• Related Disease:
  Acute myelogenous leukaemia
  Breast cancer
  Breast carcinoma
  Colitis
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Gastric cancer
  Hepatocellular carcinoma
  Leukemia
  Mantle cell lymphoma
  Neoplasm
  Stomach cancer
  Thyroid gland papillary carcinoma
  Clear cell renal carcinoma
  Pancreatic cancer
  Advanced cancer
  Lung cancer
  Lung carcinoma
• UniProt ID: SOX12_HUMAN
• Pfam ID: PF00505
• Sequence:
  MVQQRGARAKRDGGPPPPGPGPAEEGAREPGWCKTPSGHIKRPMNAFMVWSQHERRKIMD
  QWPDMHNAEISKRLGRRWQLLQDSEKIPFVREAERLRLKHMADYPDYKYRPRKKSKGAPA
  KARPRPPGGSGGGSRLKPGPQLPGRGGRRAAGGPLGGGAAAPEDDDEDDDEELLEVRLVE
  TPGRELWRMVPAGRAARGQAERAQGPSGEGAAAAAAASPTPSEDEEPEEEEEEAAAAEEG
  EEETVASGEESLGFLSRLPPGPAGLDCSALDRDPDLQPPSGTSHFEFPDYCTPEVTEMIA
  GDWRPSSIADLVFTY
• Function: Transcription factor that binds to DNA at the consensus sequence 5'-ACCAAAG-3'. Acts as a transcriptional activator. Binds cooperatively with POU3F2/BRN2 or POU3F1/OCT6 to gene promoters, which enhances transcriptional activation. Involved in the differentiation of naive CD4-positive T-cells into peripherally induced regulatory T (pT reg) cells under inflammatory conditions. Binds to the promoter region of the FOXP3 gene and promotes its transcription, and might thereby contribute to pT reg cell differentiation in the spleen and lymph nodes during inflammation. Plays a redundant role with SOX4 and SOX11 in cell survival of developing tissues such as the neural tube, branchial arches and somites, thereby contributing to organogenesis.
• Tissue Specificity: Expressed most abundantly in the CNS . Expressed in the heart, pancreas, thymus, testis and ovary . Weakly expressed in brain, placenta, lung, liver, skeletal muscle, kidney, spleen, prostate, small intestine, colon, and peripheral blood lymphocytes .

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Colitis	DISAF7DD	Strong	Biomarker	[3]
Colon cancer	DISVC52G	Strong	Biomarker	[4]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Gastric cancer	DISXGOUK	Strong	Biomarker	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[7]
Leukemia	DISNAKFL	Strong	Altered Expression	[1]
Mantle cell lymphoma	DISFREOV	Strong	Altered Expression	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Stomach cancer	DISKIJSX	Strong	Biomarker	[6]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Altered Expression	[9]
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[10]
Pancreatic cancer	DISJC981	moderate	Biomarker	[11]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[12]
Lung cancer	DISCM4YA	Limited	Altered Expression	[13]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Transcription factor SOX-12 (SOX12).	[14]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transcription factor SOX-12 (SOX12).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription factor SOX-12 (SOX12).	[16]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription factor SOX-12 (SOX12).	[17]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transcription factor SOX-12 (SOX12).	[18]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transcription factor SOX-12 (SOX12).	[19]
Marinol	DM70IK5	Approved	Marinol increases the expression of Transcription factor SOX-12 (SOX12).	[20]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Transcription factor SOX-12 (SOX12).	[21]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transcription factor SOX-12 (SOX12).	[22]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Transcription factor SOX-12 (SOX12).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Camptothecin	DM6CHNJ	Phase 3	Camptothecin increases the methylation of Transcription factor SOX-12 (SOX12).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transcription factor SOX-12 (SOX12).	[24]

References

• [1] SOX12: a novel potential target for acute myeloid leukaemia.Br J Haematol. 2017 Feb;176(3):421-430. doi: 10.1111/bjh.14425. Epub 2016 Nov 18.
• [2] Functional analyses of microRNA-326 in breast cancer development.Biosci Rep. 2019 Jul 29;39(7):BSR20190787. doi: 10.1042/BSR20190787. Print 2019 Jul 31.
• [3] Sox12 promotes T reg differentiation in the periphery during colitis.J Exp Med. 2018 Oct 1;215(10):2509-2519. doi: 10.1084/jem.20172082. Epub 2018 Sep 6.
• [4] A novel genome-wide in vivo screen for metastatic suppressors in human colon cancer identifies the positive WNT-TCF pathway modulators TMED3 and SOX12.EMBO Mol Med. 2014 Jul;6(7):882-901. doi: 10.15252/emmm.201303799.
• [5] SOX12 promotes colorectal cancer cell proliferation and metastasis by regulating asparagine synthesis.Cell Death Dis. 2019 Mar 11;10(3):239. doi: 10.1038/s41419-019-1481-9.
• [6] Sex determining region Y-box 12 (SOX12) promotes gastric cancer metastasis by upregulating MMP7 and IGF1.Cancer Lett. 2019 Jun 28;452:103-118. doi: 10.1016/j.canlet.2019.03.035. Epub 2019 Mar 25.
• [7] MicroRNA?44 inhibits migration and invasion of hepatocellular carcinoma cells by targeting SOX12.Oncol Rep. 2018 Dec;40(6):3585-3592. doi: 10.3892/or.2018.6774. Epub 2018 Oct 8.
• [8] SOXC transcription factors in mantle cell lymphoma: the role of promoter methylation in SOX11 expression.Sci Rep. 2013;3:1400. doi: 10.1038/srep01400.
• [9] NR2F1-AS1 regulated miR-423-5p/SOX12 to promote proliferation and invasion of papillary thyroid carcinoma.J Cell Biochem. 2020 Feb;121(2):2009-2018. doi: 10.1002/jcb.29435. Epub 2019 Nov 6.
• [10] SOX2 and SOX12 are predictive of prognosis in patients with clear cell renal cell carcinoma.Oncol Lett. 2018 Apr;15(4):4564-4570. doi: 10.3892/ol.2018.7828. Epub 2018 Jan 19.
• [11] MiR-29b suppresses proliferation and mobility by targeting SOX12 and DNMT3b in pancreatic cancer.Anticancer Drugs. 2019 Mar;30(3):281-288. doi: 10.1097/CAD.0000000000000719.
• [12] Sox12 Is a Cancer Stem-Like Cell Marker in Hepatocellular Carcinoma.Mol Cells. 2017 Nov 30;40(11):847-854. doi: 10.14348/molcells.2017.0129. Epub 2017 Nov 10.
• [13] Knockdown of SOX12 expression inhibits the proliferation and metastasis of lung cancer cells.Am J Transl Res. 2017 Sep 15;9(9):4003-4014. eCollection 2017.
• [14] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [15] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [16] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [17] 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.
• [18] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [19] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [20] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [21] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [22] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [23] 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.
• [24] 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.
• [25] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.