Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNNBAS1)

• DOT Name: Protein reprimo (RPRM)
• Gene Name: RPRM
• Related Disease:
  Gastric neoplasm
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Barrett esophagus
  Esophageal cancer
  Gastric cancer
  Lung cancer
  Lung carcinoma
  Neoplasm
  Neoplasm of esophagus
  Stomach cancer
  Bone osteosarcoma
  Osteosarcoma
• UniProt ID: RPRM_HUMAN
• Sequence:
  MNPALGNQTDVAGLFLANSSEALERAVRCCTQASVVTDDGFAEGGPDERSLYIMRVVQIA
  VMCVLSLTVVFGIFFLGCNLLIKSEGMINFLVKDRRPSKEVEAVVVGPY
• Function: May be involved in the regulation of p53-dependent G2 arrest of the cell cycle. Seems to induce cell cycle arrest by inhibiting CDK1 activity and nuclear translocation of the CDC2 cyclin B1 complex.
• KEGG Pathway: p53 sig.ling pathway (hsa04115)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric neoplasm	DISOKN4Y	Definitive	Posttranslational Modification	[1]
Acute monocytic leukemia	DIS28NEL	Strong	Posttranslational Modification	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Posttranslational Modification	[2]
Barrett esophagus	DIS416Y7	Strong	Biomarker	[3]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[3]
Gastric cancer	DISXGOUK	Strong	Posttranslational Modification	[4]
Lung cancer	DISCM4YA	Strong	Altered Expression	[5]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[3]
Stomach cancer	DISKIJSX	Strong	Posttranslational Modification	[4]
Bone osteosarcoma	DIST1004	moderate	Altered Expression	[6]
Osteosarcoma	DISLQ7E2	moderate	Altered Expression	[6]

2 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 Protein reprimo (RPRM).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein reprimo (RPRM).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein reprimo (RPRM).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein reprimo (RPRM).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein reprimo (RPRM).	[10]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Protein reprimo (RPRM).	[11]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Protein reprimo (RPRM).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Protein reprimo (RPRM).	[11]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Protein reprimo (RPRM).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein reprimo (RPRM).	[15]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Protein reprimo (RPRM).	[16]

References

• [1] Reprimo as a potential biomarker for early detection in gastric cancer.Clin Cancer Res. 2008 Oct 1;14(19):6264-9. doi: 10.1158/1078-0432.CCR-07-4522.
• [2] tp53-dependent G2 arrest mediator candidate gene, Reprimo, is down-regulated by promoter hypermethylation in pediatric acute myeloid leukemia.Leuk Lymphoma. 2015;56(10):2931-44. doi: 10.3109/10428194.2015.1011157. Epub 2015 Feb 24.
• [3] Reprimo methylation is a potential biomarker of Barrett's-Associated esophageal neoplastic progression.Clin Cancer Res. 2006 Nov 15;12(22):6637-42. doi: 10.1158/1078-0432.CCR-06-1781.
• [4] The relationship between DNA methylation and Reprimo gene expression in gastric cancer cells.Oncotarget. 2017 Sep 28;8(65):108610-108623. doi: 10.18632/oncotarget.21296. eCollection 2017 Dec 12.
• [5] SOX9 dependent FOXA1 expression promotes tumorigenesis in lung carcinoma.Biochem Biophys Res Commun. 2019 Aug 13;516(1):236-244. doi: 10.1016/j.bbrc.2019.05.169. Epub 2019 Jun 17.
• [6] MEF2D overexpression contributes to the progression of osteosarcoma.Gene. 2015 Jun 1;563(2):130-5. doi: 10.1016/j.gene.2015.03.046. Epub 2015 Mar 23.
• [7] 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.
• [8] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [9] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [10] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [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] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] 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.