Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCQ8DAD)

• DOT Name: Migration and invasion enhancer 1 (MIEN1)
• Synonyms: HBV X-transactivated gene 4 protein; HBV XAg-transactivated protein 4; Protein C35
• Gene Name: MIEN1
• Related Disease:
  Adenocarcinoma
  Breast lobular carcinoma
  Breast neoplasm
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Oral cancer
  Breast cancer
  Metastatic malignant neoplasm
  Neoplasm
  Gastric neoplasm
  Breast carcinoma
  Systemic lupus erythematosus
• UniProt ID: MIEN1_HUMAN
• PDB ID: 2LJK
• Pfam ID: PF10262
• Sequence:
  MSGEPGQTSVAPPPEEVEPGSGVRIVVEYCEPCGFEATYLELASAVKEQYPGIEIESRLG
  GTGAFEIEINGQLVFSKLENGGFPYEKDLIEAIRRASNGETLEKITNSRPPCVIL
• Function: Increases cell migration by inducing filopodia formation at the leading edge of migrating cells. Plays a role in regulation of apoptosis, possibly through control of CASP3. May be involved in a redox-related process.
• Tissue Specificity: Among normal tissues, present only in Leydig cells. Strongly up-regulated in breast cancers and in brain cancer distant metastasis (at protein level). Up-regulated in prostate cancer cells and in the higher grades of prostate adenocarcinoma (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[1]
Breast lobular carcinoma	DISBY98Q	Strong	Altered Expression	[2]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[3]
Colon cancer	DISVC52G	Strong	Altered Expression	[4]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[5]
Oral cancer	DISLD42D	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	moderate	Biomarker	[3]
Metastatic malignant neoplasm	DIS86UK6	moderate	Altered Expression	[7]
Neoplasm	DISZKGEW	moderate	Altered Expression	[3]
Gastric neoplasm	DISOKN4Y	Disputed	Genetic Variation	[8]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[3]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[9]

8 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 Migration and invasion enhancer 1 (MIEN1).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Migration and invasion enhancer 1 (MIEN1).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Migration and invasion enhancer 1 (MIEN1).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Migration and invasion enhancer 1 (MIEN1).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Migration and invasion enhancer 1 (MIEN1).	[14]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Migration and invasion enhancer 1 (MIEN1).	[15]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Migration and invasion enhancer 1 (MIEN1).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Migration and invasion enhancer 1 (MIEN1).	[18]

1 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 increases the methylation of Migration and invasion enhancer 1 (MIEN1).	[17]

References

• [1] Migration and Invasion Enhancer 1 Is an NF-B-Inducing Gene Enhancing the Cell Proliferation and Invasion Ability of Human Prostate Carcinoma Cells In Vitro and In Vivo.Cancers (Basel). 2019 Oct 2;11(10):1486. doi: 10.3390/cancers11101486.
• [2] C35 (C17orf37) is a novel tumor biomarker abundantly expressed in breast cancer.Mol Cancer Ther. 2006 Nov;5(11):2919-30. doi: 10.1158/1535-7163.MCT-06-0389.
• [3] CRISPR deletion of MIEN1 in breast cancer cells.PLoS One. 2018 Oct 4;13(10):e0204976. doi: 10.1371/journal.pone.0204976. eCollection 2018.
• [4] miR-136 targets MIEN1 and involves the metastasis of colon cancer by suppressing epithelial-to-mesenchymal transition.Onco Targets Ther. 2017 Dec 22;11:67-74. doi: 10.2147/OTT.S113359. eCollection 2018.
• [5] C35 is overexpressed in colorectal cancer and is associated tumor invasion and metastasis.Biosci Trends. 2015 Apr;9(2):117-21. doi: 10.5582/bst.2015.01057.
• [6] MIEN1 promotes oral cancer progression and implicates poor overall survival.Cancer Biol Ther. 2015;16(6):876-85. doi: 10.1080/15384047.2015.1040962.
• [7] MIEN1, a novel interactor of Annexin A2, promotes tumor cell migration by enhancing AnxA2 cell surface expression.Mol Cancer. 2015 Aug 15;14:156. doi: 10.1186/s12943-015-0428-8.
• [8] MGC9753 gene, located within PPP1R1B-STARD3-ERBB2-GRB7 amplicon on human chromosome 17q12, encodes the seven-transmembrane receptor with extracellular six-cystein domain.Int J Oncol. 2003 Jun;22(6):1369-74.
• [9] Transancestral mapping and genetic load in systemic lupus erythematosus.Nat Commun. 2017 Jul 17;8:16021. doi: 10.1038/ncomms16021.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [12] 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.
• [13] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [14] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [15] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [16] Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
• [17] 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.
• [18] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.