Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8ULELL)

• DOT Name: Melanoma-associated antigen 12 (MAGEA12)
• Synonyms: Cancer/testis antigen 1.12; CT1.12; MAGE-12 antigen; MAGE12F antigen
• Gene Name: MAGEA12
• Related Disease:
  Advanced cancer
  Gastric cancer
  Melanoma
  Breast cancer
  Breast carcinoma
  Cutaneous squamous cell carcinoma
  Squamous cell carcinoma
• UniProt ID: MAGAC_HUMAN
• Pfam ID: PF01454 ; PF12440
• Sequence:
  MPLEQRSQHCKPEEGLEAQGEALGLVGAQAPATEEQETASSSSTLVEVTLREVPAAESPS
  PPHSPQGASTLPTTINYTLWSQSDEGSSNEEQEGPSTFPDLETSFQVALSRKMAELVHFL
  LLKYRAREPFTKAEMLGSVIRNFQDFFPVIFSKASEYLQLVFGIEVVEVVRIGHLYILVT
  CLGLSYDGLLGDNQIVPKTGLLIIVLAIIAKEGDCAPEEKIWEELSVLEASDGREDSVFA
  HPRKLLTQDLVQENYLEYRQVPGSDPACYEFLWGPRALVETSYVKVLHHLLKISGGPHIS
  YPPLHEWAFREGEE
• Function: Not known, though may play a role tumor transformation or progression. In vitro promotes cell viability in melanoma cell lines.
• Tissue Specificity: Expressed in many tumors of several types, such as melanoma, head and neck squamous cell carcinoma, lung carcinoma and breast carcinoma, but not in normal tissues except for testes.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Gastric cancer	DISXGOUK	Strong	Posttranslational Modification	[1]
Melanoma	DIS1RRCY	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Limited	Biomarker	[3]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[3]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Biomarker	[4]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[5]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Melanoma-associated antigen 12 (MAGEA12) affects the response to substance of Etoposide.	[12]
Mitomycin	DMH0ZJE	Approved	Melanoma-associated antigen 12 (MAGEA12) affects the response to substance of Mitomycin.	[12]

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 Melanoma-associated antigen 12 (MAGEA12).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Melanoma-associated antigen 12 (MAGEA12).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Melanoma-associated antigen 12 (MAGEA12).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Melanoma-associated antigen 12 (MAGEA12).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Melanoma-associated antigen 12 (MAGEA12).	[9]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Melanoma-associated antigen 12 (MAGEA12).	[10]

References

• [1] Identification of MAGEA12 as a prognostic outlier gene in gastric cancers.Neoplasma. 2017;64(2):238-243. doi: 10.4149/neo_2017_210.
• [2] A tumor-infiltrating lymphocyte from a melanoma metastasis with decreased expression of melanoma differentiation antigens recognizes MAGE-12.J Immunol. 2000 Apr 15;164(8):4382-92. doi: 10.4049/jimmunol.164.8.4382.
• [3] Breast conserving therapy after neoadjuvant chemotherapy; data from the Dutch Breast Cancer Audit.Eur J Surg Oncol. 2019 Feb;45(2):110-117. doi: 10.1016/j.ejso.2018.09.027. Epub 2018 Oct 17.
• [4] Overexpression and Implications of Melanoma-associated Antigen A12 in Pathogenesis of Human Cutaneous Squamous Cell Carcinoma.Anticancer Res. 2019 Apr;39(4):1849-1857. doi: 10.21873/anticanres.13292.
• [5] Expression of melanoma-associated antigens in oral squamous cell carcinoma.J Oral Pathol Med. 2008 Feb;37(2):88-93. doi: 10.1111/j.1600-0714.2007.00600.x.
• [6] 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.
• [7] 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.
• [8] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [9] Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer. Mol Oncol. 2011 Oct;5(5):438-53. doi: 10.1016/j.molonc.2011.07.003. Epub 2011 Jul 26.
• [10] Dissecting progressive stages of 5-fluorouracil resistance in vitro using RNA expression profiling. Int J Cancer. 2004 Nov 1;112(2):200-12. doi: 10.1002/ijc.20401.
• [11] 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.
• [12] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.