Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAJ7R31)

• DOT Name: RNA-binding protein 3 (RBM3)
• Synonyms: RNA-binding motif protein 3; RNPL
• Gene Name: RBM3
• Related Disease:
  Cognitive impairment
  Advanced cancer
  Alzheimer disease
  Astrocytoma
  Bipolar disorder
  Breast cancer
  Breast carcinoma
  Carcinoma of esophagus
  Cluster headache
  Colitis
  Colorectal carcinoma
  Colorectal neoplasm
  Epithelial ovarian cancer
  Esophageal adenocarcinoma
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Familial multiple trichoepithelioma
  Gastric cancer
  Glioblastoma multiforme
  Inflammatory bowel disease
  Lung adenocarcinoma
  Lung cancer
  Neoplasm
  Neoplasm of esophagus
  Neuroblastoma
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Parkinson disease
  Prostate cancer
  Prostate carcinoma
  Sigmoid colon cancer
  Stomach cancer
  Triple negative breast cancer
  Breast neoplasm
  Nasopharyngeal carcinoma
  Niemann-Pick disease type C
  Pancreatic cancer
  Hepatocellular carcinoma
  Inflammatory breast cancer
  Invasive breast carcinoma
  Melanoma
  Colon cancer
  Colon carcinoma
• UniProt ID: RBM3_HUMAN
• PDB ID: 7EB1
• Pfam ID: PF00076
• Sequence:
  MSSEEGKLFVGGLNFNTDEQALEDHFSSFGPISEVVVVKDRETQRSRGFGFITFTNPEHA
  SVAMRAMNGESLDGRQIRVDHAGKSARGTRGGGFGAHGRGRSYSRGGGDQGYGSGRYYDS
  RPGGYGYGYGRSRDYNGRNQGGYDRYSGGNYRDNYDN
• Function: Cold-inducible mRNA binding protein that enhances global protein synthesis at both physiological and mild hypothermic temperatures. Reduces the relative abundance of microRNAs, when overexpressed. Enhances phosphorylation of translation initiation factors and active polysome formation.

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cognitive impairment	DISH2ERD	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Astrocytoma	DISL3V18	Strong	Biomarker	[4]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[7]
Cluster headache	DISKAXY9	Strong	Biomarker	[5]
Colitis	DISAF7DD	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[10]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[11]
Esophageal adenocarcinoma	DISODWFP	Strong	Altered Expression	[7]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[7]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[7]
Familial multiple trichoepithelioma	DISKZAUY	Strong	Altered Expression	[7]
Gastric cancer	DISXGOUK	Strong	Biomarker	[11]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[4]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[8]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[2]
Lung cancer	DISCM4YA	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[12]
Neoplasm of esophagus	DISOLKAQ	Strong	Altered Expression	[7]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[2]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[11]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[11]
Parkinson disease	DISQVHKL	Strong	Biomarker	[13]
Prostate cancer	DISF190Y	Strong	Biomarker	[14]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[14]
Sigmoid colon cancer	DISVZMTQ	Strong	Altered Expression	[15]
Stomach cancer	DISKIJSX	Strong	Biomarker	[11]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[16]
Breast neoplasm	DISNGJLM	moderate	Biomarker	[17]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Altered Expression	[18]
Niemann-Pick disease type C	DIS492ZO	moderate	Biomarker	[18]
Pancreatic cancer	DISJC981	moderate	Biomarker	[12]
Hepatocellular carcinoma	DIS0J828	Disputed	Altered Expression	[19]
Inflammatory breast cancer	DIS3QRWA	Disputed	Altered Expression	[20]
Invasive breast carcinoma	DISANYTW	Disputed	Biomarker	[20]
Melanoma	DIS1RRCY	Disputed	Altered Expression	[20]
Colon cancer	DISVC52G	Limited	Altered Expression	[20]
Colon carcinoma	DISJYKUO	Limited	Altered Expression	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of RNA-binding protein 3 (RBM3).	[21]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of RNA-binding protein 3 (RBM3).	[22]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of RNA-binding protein 3 (RBM3).	[23]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of RNA-binding protein 3 (RBM3).	[24]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of RNA-binding protein 3 (RBM3).	[25]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of RNA-binding protein 3 (RBM3).	[26]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of RNA-binding protein 3 (RBM3).	[27]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of RNA-binding protein 3 (RBM3).	[28]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of RNA-binding protein 3 (RBM3).	[29]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of RNA-binding protein 3 (RBM3).	[30]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of RNA-binding protein 3 (RBM3).	[31]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of RNA-binding protein 3 (RBM3).	[33]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of RNA-binding protein 3 (RBM3).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of RNA-binding protein 3 (RBM3).	[36]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of RNA-binding protein 3 (RBM3).	[37]

2 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 RNA-binding protein 3 (RBM3).	[32]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of RNA-binding protein 3 (RBM3).	[35]

References

• [1] RTN3 Is a Novel Cold-Induced Protein and Mediates Neuroprotective Effects of RBM3.Curr Biol. 2017 Mar 6;27(5):638-650. doi: 10.1016/j.cub.2017.01.047. Epub 2017 Feb 23.
• [2] Prevalence and clinical significance of RBM3 immunostaining in non-small cell lung cancers.J Cancer Res Clin Oncol. 2019 Apr;145(4):873-879. doi: 10.1007/s00432-019-02850-1. Epub 2019 Feb 13.
• [3] Cold Shock Induced Protein RBM3 but Not Mild Hypothermia Protects Human SH-SY5Y Neuroblastoma Cells From MPP(+)-Induced Neurotoxicity.Front Neurosci. 2018 May 3;12:298. doi: 10.3389/fnins.2018.00298. eCollection 2018.
• [4] Differential expression of the RNA-binding motif protein 3 in human astrocytoma.Chin Med J (Engl). 2013;126(10):1948-52.
• [5] Preliminary Transcriptome Analysis in Lymphoblasts from Cluster Headache and Bipolar Disorder Patients Implicates Dysregulation of Circadian and Serotonergic Genes.J Mol Neurosci. 2015 Jul;56(3):688-95. doi: 10.1007/s12031-015-0567-9. Epub 2015 Apr 28.
• [6] RBM3 upregulates ARPC2 by binding the 3'UTR and contributes to breast cancer progression.Int J Oncol. 2019 Apr;54(4):1387-1397. doi: 10.3892/ijo.2019.4698. Epub 2019 Jan 28.
• [7] Reduced RBM3 expression is associated with aggressive tumor features in esophageal cancer but not significantly linked to patient outcome.BMC Cancer. 2018 Nov 12;18(1):1106. doi: 10.1186/s12885-018-5032-z.
• [8] Stress Response Protein RBM3 Promotes the Development of Colitis-associated Cancer.Inflamm Bowel Dis. 2017 Jan;23(1):57-65. doi: 10.1097/MIB.0000000000000968.
• [9] RNA binding protein RBM3 increases -catenin signaling to increase stem cell characteristics in colorectal cancer cells.Mol Carcinog. 2016 Nov;55(11):1503-1516. doi: 10.1002/mc.22404. Epub 2015 Aug 31.
• [10] Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe.Oncogene. 2008 Jul 31;27(33):4544-56. doi: 10.1038/onc.2008.97. Epub 2008 Apr 21.
• [11] High RNA-Binding Motif Protein 3 (RBM3) Expression is Independently Associated with Prolonged Overall Survival in Intestinal-Type Gastric Cancer.Med Sci Monit. 2017 Dec 21;23:6033-6041. doi: 10.12659/msm.905314.
• [12] Translational study reveals a two-faced role of RBM3 in pancreatic cancer and suggests its potential value as a biomarker for improved patient stratification.Oncotarget. 2017 Dec 15;9(5):6188-6200. doi: 10.18632/oncotarget.23486. eCollection 2018 Jan 19.
• [13] Cold-inducible protein RBM3 mediates hypothermic neuroprotection against neurotoxin rotenone via inhibition on MAPK signalling.J Cell Mol Med. 2019 Oct;23(10):7010-7020. doi: 10.1111/jcmm.14588. Epub 2019 Aug 22.
• [14] Impact of RNAbinding motif 3 expression on the whole transcriptome of prostate cancer cells: An RNA sequencing study.Oncol Rep. 2018 Oct;40(4):2307-2315. doi: 10.3892/or.2018.6618. Epub 2018 Aug 1.
• [15] High nuclear RBM3 expression is associated with an improved prognosis in colorectal cancer.Proteomics Clin Appl. 2011 Dec;5(11-12):624-35. doi: 10.1002/prca.201100020.
• [16] LINC00096 Promotes the Proliferation and Invasion by Sponging miR-383-5p and Regulating RBM3 Expression in Triple-Negative Breast Cancer.Onco Targets Ther. 2019 Dec 2;12:10569-10578. doi: 10.2147/OTT.S229659. eCollection 2019.
• [17] Nuclear expression of the RNA-binding protein RBM3 is associated with an improved clinical outcome in breast cancer.Mod Pathol. 2009 Dec;22(12):1564-74. doi: 10.1038/modpathol.2009.124. Epub 2009 Sep 4.
• [18] RNA binding motif protein 3 (RBM3) drives radioresistance in nasopharyngeal carcinoma by reducing apoptosis via the PI3K/AKT/Bcl-2 signaling pathway.Am J Transl Res. 2018 Dec 15;10(12):4130-4140. eCollection 2018.
• [19] The RNA-binding protein RBM3 promotes cell proliferation in hepatocellular carcinoma by regulating circular RNA SCD-circRNA 2 production.EBioMedicine. 2019 Jul;45:155-167. doi: 10.1016/j.ebiom.2019.06.030. Epub 2019 Jun 22.
• [20] High RNA-binding Motif Protein 3 Expression Is Associated with Improved Clinical Outcomes in Invasive Breast Cancer.J Breast Cancer. 2018 Sep;21(3):288-296. doi: 10.4048/jbc.2018.21.e34. Epub 2018 Aug 28.
• [21] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [22] 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.
• [23] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [24] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [25] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [26] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [27] 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.
• [28] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [29] 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.
• [30] 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.
• [31] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [32] 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.
• [33] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [34] 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.
• [35] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [36] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [37] Suppression subtractive hybridization identifies high glucose levels as a stimulus for expression of connective tissue growth factor and other genes in human mesangial cells. J Biol Chem. 1999 Feb 26;274(9):5830-4. doi: 10.1074/jbc.274.9.5830.