Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA96YEL)

• DOT Name: Transmembrane protein 88 (TMEM88)
• Gene Name: TMEM88
• Related Disease:
  Advanced cancer
  Epithelial ovarian cancer
  Lung cancer
  Lung carcinoma
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Triple negative breast cancer
  Breast cancer
  Breast carcinoma
  Neoplasm
• UniProt ID: TMM88_HUMAN
• Sequence:
  MADVPGAQRAVPGDGPEPRDPLDCWACAVLVTAQNLLVAAFNLLLLVLVLGTILLPAVTM
  LGFGFLCHSQFLRSQAPPCTAHLRDPGFTALLVTGFLLLVPLLVLALASYRRLCLRLRLA
  DCLVPYSRALYRRRRAPQPRQIRASPGSQAVPTSGKVWV
• Function: Inhibits the Wnt/beta-catenin signaling pathway. Crucial for heart development and acts downstream of GATA factors in the pre-cardiac mesoderm to specify lineage commitment of cardiomyocyte development.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[2]
Lung cancer	DISCM4YA	Strong	Biomarker	[3]
Lung carcinoma	DISTR26C	Strong	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[4]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[2]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[2]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Disputed	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Disputed	Altered Expression	[1]
Neoplasm	DISZKGEW	Disputed	Biomarker	[1]

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 Transmembrane protein 88 (TMEM88).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Transmembrane protein 88 (TMEM88).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transmembrane protein 88 (TMEM88).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transmembrane protein 88 (TMEM88).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transmembrane protein 88 (TMEM88).	[9]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Transmembrane protein 88 (TMEM88).	[10]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Transmembrane protein 88 (TMEM88).	[11]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Transmembrane protein 88 (TMEM88).	[12]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of Transmembrane protein 88 (TMEM88).	[13]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Transmembrane protein 88 (TMEM88).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Transmembrane protein 88 (TMEM88).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transmembrane protein 88 (TMEM88).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Transmembrane protein 88 (TMEM88).	[17]

References

• [1] New advances of TMEM88 in cancer initiation and progression, with special emphasis on Wnt signaling pathway.J Cell Physiol. 2018 Jan;233(1):79-87. doi: 10.1002/jcp.25853. Epub 2017 Apr 27.
• [2] Transmembrane protein 88 (TMEM88) promoter hypomethylation is associated with platinum resistance in ovarian cancer.Gynecol Oncol. 2016 Sep;142(3):539-47. doi: 10.1016/j.ygyno.2016.06.017. Epub 2016 Jun 30.
• [3] Increased miR-708 expression in NSCLC and its association with poor survival in lung adenocarcinoma from never smokers.Clin Cancer Res. 2012 Jul 1;18(13):3658-67. doi: 10.1158/1078-0432.CCR-11-2857. Epub 2012 May 9.
• [4] TMEM206 promotes the malignancy of colorectal cancer cells by interacting with AKT and extracellular signal-regulated kinase signaling pathways.J Cell Physiol. 2019 Jul;234(7):10888-10898. doi: 10.1002/jcp.27751. Epub 2018 Nov 11.
• [5] Cytosolic TMEM88 promotes triple-negative breast cancer by interacting with Dvl.Oncotarget. 2015 Sep 22;6(28):25034-45. doi: 10.18632/oncotarget.4379.
• [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] 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.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Research resource: STR DNA profile and gene expression comparisons of human BG-1 cells and a BG-1/MCF-7 clonal variant. Mol Endocrinol. 2014 Dec;28(12):2072-81.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] 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.
• [12] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [13] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [14] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [15] 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.
• [16] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [17] 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.