Details of Drug Off-Target (DOT)

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

• DOT Name: Thymosin beta-15A (TMSB15A)
• Synonyms: NB thymosin beta; Thymosin-like protein 8
• Gene Name: TMSB15A
• Related Disease:
  Neuroblastoma
  Triple negative breast cancer
  Lung neoplasm
  Prostate neoplasm
  HIV infectious disease
  Tuberculosis
  Cervical cancer
  Cervical carcinoma
  Prostate cancer
  Prostate carcinoma
• UniProt ID: TB15A_HUMAN
• Pfam ID: PF01290
• Sequence: MSDKPDLSEVEKFDRSKLKKTNTEEKNTLPSKETIQQEKECVQTS
• Function: Plays an important role in the organization of the cytoskeleton. Binds to and sequesters actin monomers (G actin) and therefore inhibits actin polymerization.
• Tissue Specificity: Neuroblastoma-specific.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neuroblastoma	DISVZBI4	Definitive	Altered Expression	[1]
Triple negative breast cancer	DISAMG6N	Definitive	Altered Expression	[2]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[3]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[4]
HIV infectious disease	DISO97HC	Disputed	Biomarker	[5]
Tuberculosis	DIS2YIMD	Disputed	Biomarker	[5]
Cervical cancer	DISFSHPF	Limited	Altered Expression	[6]
Cervical carcinoma	DIST4S00	Limited	Altered Expression	[6]
Prostate cancer	DISF190Y	Limited	Biomarker	[7]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[7]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Thymosin beta-15A (TMSB15A) affects the response to substance of Fluorouracil.	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Thymosin beta-15A (TMSB15A).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Thymosin beta-15A (TMSB15A).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Thymosin beta-15A (TMSB15A).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Thymosin beta-15A (TMSB15A).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Thymosin beta-15A (TMSB15A).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Thymosin beta-15A (TMSB15A).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Thymosin beta-15A (TMSB15A).	[13]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Thymosin beta-15A (TMSB15A).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Thymosin beta-15A (TMSB15A).	[14]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Thymosin beta-15A (TMSB15A).	[15]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Thymosin beta-15A (TMSB15A).	[16]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Thymosin beta-15A (TMSB15A).	[17]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Thymosin beta-15A (TMSB15A).	[18]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Thymosin beta-15A (TMSB15A).	[19]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Thymosin beta-15A (TMSB15A).	[20]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Thymosin beta-15A (TMSB15A).	[21]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Thymosin beta-15A (TMSB15A).	[16]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Thymosin beta-15A (TMSB15A).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Thymosin beta-15A (TMSB15A).	[24]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Thymosin beta-15A (TMSB15A).	[25]

References

• [1] Functional and profiling studies prove that prostate cancer upregulated neuroblastoma thymosin beta is the true human homologue of rat thymosin beta15.FEBS Lett. 2007 Oct 16;581(25):4809-15. doi: 10.1016/j.febslet.2007.09.003. Epub 2007 Sep 12.
• [2] Thymosin beta 15A (TMSB15A) is a predictor of chemotherapy response in triple-negative breast cancer.Br J Cancer. 2012 Nov 20;107(11):1892-900. doi: 10.1038/bjc.2012.475. Epub 2012 Oct 18.
• [3] Elevated thymosin beta15 expression is associated with progression and metastasis of non-small cell lung cancer.APMIS. 2008 Jun;116(6):484-90. doi: 10.1111/j.1600-0463.2008.00918.x.
• [4] Thymosin beta 15: a novel regulator of tumor cell motility upregulated in metastatic prostate cancer.Nat Med. 1996 Dec;2(12):1322-8. doi: 10.1038/nm1296-1322.
• [5] Xpert MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults.Cochrane Database Syst Rev. 2013 Jan 31;(1):CD009593. doi: 10.1002/14651858.CD009593.pub2.
• [6] Gene dosage alterations revealed by cDNA microarray analysis in cervical cancer: identification of candidate amplified and overexpressed genes.Genes Chromosomes Cancer. 2007 Apr;46(4):373-84. doi: 10.1002/gcc.20418.
• [7] The mouse thymosin beta15 gene family displays unique complexity and encodes a functional thymosin repeat.J Mol Biol. 2009 Apr 10;387(4):809-25. doi: 10.1016/j.jmb.2009.02.026. Epub 2009 Feb 20.
• [8] 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.
• [9] 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.
• [10] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [11] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [12] Identification of novel gene targets and putative regulators of arsenic-associated DNA methylation in human urothelial cells and bladder cancer. Chem Res Toxicol. 2015 Jun 15;28(6):1144-55. doi: 10.1021/tx500393y. Epub 2015 Jun 3.
• [13] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [14] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [15] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [16] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [17] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [18] 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.
• [19] Chronic ethanol exposure increases goosecoid (GSC) expression in human embryonic carcinoma cell differentiation. J Appl Toxicol. 2014 Jan;34(1):66-75.
• [20] 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.
• [21] 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.
• [22] 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.
• [23] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [24] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [25] 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.
• [26] Molecular characterizations of derivatives of HCT116 colorectal cancer cells that are resistant to the chemotherapeutic agent 5-fluorouracil. Int J Oncol. 2004 May;24(5):1279-88.