Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPO8EXU)

• DOT Name: RNA-binding protein 38 (RBM38)
• Synonyms: CLL-associated antigen KW-5; HSRNASEB; RNA-binding motif protein 38; RNA-binding region-containing protein 1; ssDNA-binding protein SEB4
• Gene Name: RBM38
• Related Disease:
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Esophageal adenocarcinoma
  Estrogen-receptor positive breast cancer
  Fatty liver disease
  Hepatocellular carcinoma
  Malignant soft tissue neoplasm
  Neoplasm
  Non-small-cell lung cancer
  Renal cell carcinoma
  Anemia
  Hydrops fetalis
  Advanced cancer
  Carcinoma of liver and intrahepatic biliary tract
  Epithelial ovarian cancer
  Liver cancer
  Lymphoma
  Ovarian cancer
  Ovarian neoplasm
• UniProt ID: RBM38_HUMAN
• PDB ID: 2CQD; 6JVX; 6JVY
• Pfam ID: PF00076
• Sequence:
  MLLQPAPCAPSAGFPRPLAAPGAMHGSQKDTTFTKIFVGGLPYHTTDASLRKYFEGFGDI
  EEAVVITDRQTGKSRGYGFVTMADRAAAERACKDPNPIIDGRKANVNLAYLGAKPRSLQT
  GFAIGVQQLHPTLIQRTYGLTPHYIYPPAIVQPSVVIPAAPVPSLSSPYIEYTPASPAYA
  QYPPATYDQYPYAASPATAASFVGYSYPAAVPQALSAAAPAGTTFVQYQAPQLQPDRMQ
• Function: RNA-binding protein that specifically bind the 3'-UTR of CDKN1A transcripts, leading to maintain the stability of CDKN1A transcripts, thereby acting as a mediator of the p53/TP53 family to regulate CDKN1A. CDKN1A is a cyclin-dependent kinase inhibitor transcriptionally regulated by the p53/TP53 family to induce cell cycle arrest. Isoform 1, but not isoform 2, has the ability to induce cell cycle arrest in G1 and maintain the stability of CDKN1A transcripts induced by p53/TP53. Also acts as a mRNA splicing factor. Specifically regulates the expression of FGFR2-IIIb, an epithelial cell-specific isoform of FGFR2. Plays a role in myogenic differentiation; (Microbial infection) Essential factor for the splicing of the pre-mRNAs of human parvovirus B19 (B19V) and for the expression of B19V 11-kDa protein, which enhances viral replication.

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[3]
Colon cancer	DISVC52G	Strong	Altered Expression	[4]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[4]
Esophageal adenocarcinoma	DISODWFP	Strong	Biomarker	[5]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Altered Expression	[6]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[8]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Altered Expression	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[11]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[3]
Anemia	DISTVL0C	moderate	Genetic Variation	[12]
Hydrops fetalis	DISD9BBF	moderate	Genetic Variation	[12]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[10]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Altered Expression	[8]
Epithelial ovarian cancer	DIS56MH2	Limited	Altered Expression	[13]
Liver cancer	DISDE4BI	Limited	Altered Expression	[8]
Lymphoma	DISN6V4S	Limited	Altered Expression	[14]
Ovarian cancer	DISZJHAP	Limited	Altered Expression	[13]
Ovarian neoplasm	DISEAFTY	Limited	Altered Expression	[13]

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 RNA-binding protein 38 (RBM38).	[15]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of RNA-binding protein 38 (RBM38).	[21]

15 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 RNA-binding protein 38 (RBM38).	[16]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of RNA-binding protein 38 (RBM38).	[17]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of RNA-binding protein 38 (RBM38).	[18]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of RNA-binding protein 38 (RBM38).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of RNA-binding protein 38 (RBM38).	[20]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of RNA-binding protein 38 (RBM38).	[22]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of RNA-binding protein 38 (RBM38).	[23]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of RNA-binding protein 38 (RBM38).	[24]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of RNA-binding protein 38 (RBM38).	[25]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of RNA-binding protein 38 (RBM38).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of RNA-binding protein 38 (RBM38).	[26]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of RNA-binding protein 38 (RBM38).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of RNA-binding protein 38 (RBM38).	[28]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of RNA-binding protein 38 (RBM38).	[29]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of RNA-binding protein 38 (RBM38).	[30]

References

• [1] RNA Binding Protein RNPC1 Inhibits Breast Cancer Cell Metastasis via Activating STARD13-Correlated ceRNA Network.Mol Pharm. 2018 Jun 4;15(6):2123-2132. doi: 10.1021/acs.molpharmaceut.7b01123. Epub 2018 May 15.
• [2] RNA-binding protein RNPC1: acting as a tumor suppressor in breast cancer.BMC Cancer. 2014 May 7;14:322. doi: 10.1186/1471-2407-14-322.
• [3] The expression of RNA-binding protein RBM38 decreased in renal cell carcinoma and represses renal cancer cell proliferation, migration, and invasion.Tumour Biol. 2017 May;39(5):1010428317701635. doi: 10.1177/1010428317701635.
• [4] Cancer-related serological recognition of human colon cancer: identification of potential diagnostic and immunotherapeutic targets.Cancer Res. 2002 Jul 15;62(14):4041-7.
• [5] Radiation sensitivity of esophageal adenocarcinoma: the contribution of the RNA-binding protein RNPC1 and p21-mediated cell cycle arrest to radioresistance.Radiat Res. 2012 Mar;177(3):272-9. doi: 10.1667/rr2776.1. Epub 2012 Jan 3.
• [6] Estrogen receptor (ER) was regulated by RNPC1 stabilizing mRNA in ER positive breast cancer.Oncotarget. 2015 May 20;6(14):12264-78. doi: 10.18632/oncotarget.3654.
• [7] The Rbm38-p63 feedback loop is critical for tumor suppression and longevity.Oncogene. 2018 May;37(21):2863-2872. doi: 10.1038/s41388-018-0176-5. Epub 2018 Mar 9.
• [8] RBM38 plays a tumor-suppressor role via stabilizing the p53-mdm2 loop function in hepatocellular carcinoma.J Exp Clin Cancer Res. 2018 Sep 3;37(1):212. doi: 10.1186/s13046-018-0852-x.
• [9] Integrative genomic analyses of the RNA-binding protein, RNPC1, and its potential role in cancer prediction.Int J Mol Med. 2015 Aug;36(2):473-84. doi: 10.3892/ijmm.2015.2237. Epub 2015 Jun 5.
• [10] Disruption of the Rbm38-eIF4E Complex with a Synthetic Peptide Pep8 Increases p53 Expression.Cancer Res. 2019 Feb 15;79(4):807-818. doi: 10.1158/0008-5472.CAN-18-2209. Epub 2018 Dec 27.
• [11] RNPC1 inhibits non-small cell lung cancer progression via regulating miR-181a/CASC2 axis.Biotechnol Lett. 2018 Mar;40(3):543-550. doi: 10.1007/s10529-017-2504-1. Epub 2017 Dec 29.
• [12] RNA Binding Protein RBM38 Regulates Expression of the 11-Kilodalton Protein of Parvovirus B19, Which Facilitates Viral DNA Replication.J Virol. 2018 Mar 28;92(8):e02050-17. doi: 10.1128/JVI.02050-17. Print 2018 Apr 15.
• [13] RBM38 is a direct transcriptional target of E2F1 that limits E2F1-induced proliferation.Mol Cancer Res. 2012 Sep;10(9):1169-77. doi: 10.1158/1541-7786.MCR-12-0331. Epub 2012 Jul 13.
• [14] Translational repression of p53 by RNPC1, a p53 target overexpressed in lymphomas.Genes Dev. 2011 Jul 15;25(14):1528-43. doi: 10.1101/gad.2069311.
• [15] 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.
• [16] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [17] 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.
• [18] 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.
• [19] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [20] 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.
• [21] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [22] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [23] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [24] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [25] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [26] 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.
• [27] 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.
• [28] Bisphenol-A and estradiol exert novel gene regulation in human MCF-7 derived breast cancer cells. Mol Cell Endocrinol. 2004 Jun 30;221(1-2):47-55. doi: 10.1016/j.mce.2004.04.010.
• [29] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [30] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.