Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5U38CP)

• DOT Name: Protein maestro (MRO)
• Synonyms: Male-specific transcription in the developing reproductive organs; Protein B29
• Gene Name: MRO
• Related Disease:
  Hepatocellular carcinoma
  Bacillary dysentery
  Carcinoma
  Haematological malignancy
  Lung neoplasm
  Polycystic ovarian syndrome
  Small lymphocytic lymphoma
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid gland undifferentiated (anaplastic) carcinoma
  Thyroid tumor
  Thyroid gland follicular carcinoma
  Undifferentiated carcinoma
  Advanced cancer
  Neoplasm
• UniProt ID: MSTRO_HUMAN
• Pfam ID: PF21047
• Sequence:
  MDQRQRRILGQPLSIPTSQPKQKRTSMISFFSKVSWKLRFQKREPLKNVFFILAERARDP
  SAKKRHMAMRNLGTMAYEAPDKVRKYKKIVLDLLVYGLYDPVNLEVIHESMKTLTVVLGK
  IQGKGLGSFFIDITLQTRTLLDDENDSLRYSAFVLFGQLAAFAGRKWKKFFTSQVKQTRD
  SLLIHLQDRNPQVAKACKTTFQACSPYLKLKEEYSFQSEEDQRNTKLYQQLSHYHPEILQ
  FFYANKIL
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Bacillary dysentery	DISFZHKN	Strong	Biomarker	[2]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[3]
Haematological malignancy	DISCDP7W	Strong	Altered Expression	[4]
Lung neoplasm	DISVARNB	Strong	Biomarker	[5]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Altered Expression	[6]
Small lymphocytic lymphoma	DIS30POX	Strong	Genetic Variation	[7]
Thyroid cancer	DIS3VLDH	Strong	Biomarker	[8]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[8]
Thyroid gland undifferentiated (anaplastic) carcinoma	DISYBB1W	Strong	Biomarker	[3]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[8]
Thyroid gland follicular carcinoma	DISFK2QT	moderate	Biomarker	[9]
Undifferentiated carcinoma	DISIAZST	moderate	Biomarker	[9]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[10]
Neoplasm	DISZKGEW	Limited	Biomarker	[11]

9 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 Protein maestro (MRO).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein maestro (MRO).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein maestro (MRO).	[14]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Protein maestro (MRO).	[15]
Marinol	DM70IK5	Approved	Marinol increases the expression of Protein maestro (MRO).	[16]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate decreases the expression of Protein maestro (MRO).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein maestro (MRO).	[19]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Protein maestro (MRO).	[20]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Protein maestro (MRO).	[21]

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 affects the methylation of Protein maestro (MRO).	[18]

References

• [1] Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells initro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology. 2017 Jun;152(8):2022-2036.
• [2] The Orchestra and Its Maestro: Shigella's Fine-Tuning of the Inflammasome Platforms.Curr Top Microbiol Immunol. 2016;397:91-115. doi: 10.1007/978-3-319-41171-2_5.
• [3] Somatostatin receptor subtype expression in human thyroid and thyroid carcinoma cell lines.J Clin Endocrinol Metab. 1997 Jun;82(6):1857-62. doi: 10.1210/jcem.82.6.4013.
• [4] Transcription and protein expression of mb-1 and B29 genes in human hematopoietic malignancies and cell lines.Leukemia. 1993 Dec;7(12):1939-47.
• [5] Lung tumor segmentation methods: Impact on the uncertainty of radiomics features for non-small cell lung cancer.PLoS One. 2018 Oct 4;13(10):e0205003. doi: 10.1371/journal.pone.0205003. eCollection 2018.
• [6] The elusive MAESTRO gene: Its human reproductive tissue-specific expression pattern.PLoS One. 2017 Apr 13;12(4):e0174873. doi: 10.1371/journal.pone.0174873. eCollection 2017.
• [7] Widespread B29 (CD79b) gene defects and loss of expression in chronic lymphocytic leukemia.Leuk Lymphoma. 1999 Feb;32(5-6):561-9. doi: 10.3109/10428199909058414.
• [8] HLA-DR alpha gene regulation in immortalized human thyroid cancer cells.Clin Immunol Immunopathol. 1993 May;67(2):151-6. doi: 10.1006/clin.1993.1058.
• [9] Vitamin D less-calcemic analog modulates the expression of estrogen receptors, vitamin D receptor and 1-hydroxylase 25-hydroxy vitamin D in human thyroid cancer cell lines.J Steroid Biochem Mol Biol. 2013 Jul;136:80-2. doi: 10.1016/j.jsbmb.2012.09.015. Epub 2012 Oct 8.
• [10] Ataxia-Telangiectasia Mutated Kinase in the Control of Oxidative Stress, Mitochondria, and Autophagy in Cancer: A Maestro With a Large Orchestra.Front Oncol. 2018 Mar 16;8:73. doi: 10.3389/fonc.2018.00073. eCollection 2018.
• [11] Registration error of the liver CT using deformable image registration of MIM Maestro and Velocity AI.BMC Med Imaging. 2017 May 4;17(1):30. doi: 10.1186/s12880-017-0202-z.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [13] 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.
• [14] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [15] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [16] 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.
• [17] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [18] 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.
• [19] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [20] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [21] 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.