Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFU3OEZ)

• DOT Name: Heterogeneous nuclear ribonucleoprotein M (HNRNPM)
• Synonyms: hnRNP M
• Gene Name: HNRNPM
• Related Disease:
  Benign prostatic hyperplasia
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Malignant soft tissue neoplasm
  Neoplasm
  Non-alcoholic fatty liver disease
  Prostate cancer
  Prostate carcinoma
  Sarcoma
  Triple negative breast cancer
  Coronary heart disease
  Prader-Willi syndrome
  Advanced cancer
  Metastatic malignant neoplasm
• UniProt ID: HNRPM_HUMAN
• PDB ID: 2DGV; 2DH9; 2DO0; 2OT8
• Pfam ID: PF11532 ; PF00076
• Sequence:
  MAAGVEAAAEVAATEIKMEEESGAPGVPSGNGAPGPKGEGERPAQNEKRKEKNIKRGGNR
  FEPYANPTKRYRAFITNIPFDVKWQSLKDLVKEKVGEVTYVELLMDAEGKSRGCAVVEFK
  MEESMKKAAEVLNKHSLSGRPLKVKEDPDGEHARRAMQKVMATTGGMGMGPGGPGMITIP
  PSILNNPNIPNEIIHALQAGRLGSTVFVANLDYKVGWKKLKEVFSMAGVVVRADILEDKD
  GKSRGIGTVTFEQSIEAVQAISMFNGQLLFDRPMHVKMDERALPKGDFFPPERPQQLPHG
  LGGIGMGLGPGGQPIDANHLNKGIGMGNIGPAGMGMEGIGFGINKMGGMEGPFGGGMENM
  GRFGSGMNMGRINEILSNALKRGEIIAKQGGGGGGGSVPGIERMGPGIDRLGGAGMERMG
  AGLGHGMDRVGSEIERMGLVMDRMGSVERMGSGIERMGPLGLDHMASSIERMGQTMERIG
  SGVERMGAGMGFGLERMAAPIDRVGQTIERMGSGVERMGPAIERMGLSMERMVPAGMGAG
  LERMGPVMDRMATGLERMGANNLERMGLERMGANSLERMGLERMGANSLERMGPAMGPAL
  GAGIERMGLAMGGGGGASFDRAIEMERGNFGGSFAGSFGGAGGHAPGVARKACQIFVRNL
  PFDFTWKMLKDKFNECGHVLYADIKMENGKSKGCGVVKFESPEVAERACRMMNGMKLSGR
  EIDVRIDRNA
• Function: Pre-mRNA binding protein in vivo, binds avidly to poly(G) and poly(U) RNA homopolymers in vitro. Involved in splicing. Acts as a receptor for carcinoembryonic antigen in Kupffer cells, may initiate a series of signaling events leading to tyrosine phosphorylation of proteins and induction of IL-1 alpha, IL-6, IL-10 and tumor necrosis factor alpha cytokines.
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway:
  mRNA Splicing - Major Pathway (R-HSA-72163)
  Processing of Capped Intron-Containing Pre-mRNA (R-HSA-72203)
  FGFR2 alternative splicing (R-HSA-6803529)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Colon cancer	DISVC52G	Strong	Biomarker	[3]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[4]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Altered Expression	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[6]
Prostate cancer	DISF190Y	Strong	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[1]
Sarcoma	DISZDG3U	Strong	Altered Expression	[5]
Triple negative breast cancer	DISAMG6N	Strong	Genetic Variation	[7]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[8]
Prader-Willi syndrome	DISYWMLU	moderate	Biomarker	[9]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[3]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Heterogeneous nuclear ribonucleoprotein M (HNRNPM) affects the response to substance of Doxorubicin.	[26]

12 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 Heterogeneous nuclear ribonucleoprotein M (HNRNPM).	[11]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Heterogeneous nuclear ribonucleoprotein M (HNRNPM).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Heterogeneous nuclear ribonucleoprotein M (HNRNPM).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heterogeneous nuclear ribonucleoprotein M (HNRNPM).	[14]
Selenium	DM25CGV	Approved	Selenium increases the expression of Heterogeneous nuclear ribonucleoprotein M (HNRNPM).	[16]
Etretinate	DM2CZFA	Approved	Etretinate decreases the expression of Heterogeneous nuclear ribonucleoprotein M (HNRNPM).	[17]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Heterogeneous nuclear ribonucleoprotein M (HNRNPM).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Heterogeneous nuclear ribonucleoprotein M (HNRNPM).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Heterogeneous nuclear ribonucleoprotein M (HNRNPM).	[20]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Heterogeneous nuclear ribonucleoprotein M (HNRNPM).	[23]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Heterogeneous nuclear ribonucleoprotein M (HNRNPM).	[24]
(E)-4-(3,5-dimethoxystyryl)phenol	DMYXI2V	Investigative	(E)-4-(3,5-dimethoxystyryl)phenol increases the expression of Heterogeneous nuclear ribonucleoprotein M (HNRNPM).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Heterogeneous nuclear ribonucleoprotein M (HNRNPM).	[15]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Heterogeneous nuclear ribonucleoprotein M (HNRNPM).	[19]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Heterogeneous nuclear ribonucleoprotein M (HNRNPM).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Heterogeneous nuclear ribonucleoprotein M (HNRNPM).	[22]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Heterogeneous nuclear ribonucleoprotein M (HNRNPM).	[21]

References

• [1] hnRNPM, a potential mediator of YY1 in promotingthe epithelial-mesenchymal transition of prostate cancer cells.Prostate. 2019 Aug;79(11):1199-1210. doi: 10.1002/pros.23790.
• [2] Heterogeneous nuclear ribonucleoprotein M promotes the progression of breast cancer by regulating the axin/-catenin signaling pathway.Biomed Pharmacother. 2018 Sep;105:848-855. doi: 10.1016/j.biopha.2018.05.014. Epub 2018 Jun 18.
• [3] hnRNPM induces translation switch under hypoxia to promote colon cancer development.EBioMedicine. 2019 Mar;41:299-309. doi: 10.1016/j.ebiom.2019.02.059. Epub 2019 Mar 7.
• [4] Carcinoembryonic antigen-stimulated THP-1 macrophages activate endothelial cells and increase cell-cell adhesion of colorectal cancer cells.Clin Exp Metastasis. 2007;24(3):201-9. doi: 10.1007/s10585-007-9069-7. Epub 2007 May 9.
• [5] hnRNPM guides an alternative splicing program in response to inhibition of the PI3K/AKT/mTOR pathway in Ewing sarcoma cells.Nucleic Acids Res. 2017 Dec 1;45(21):12270-12284. doi: 10.1093/nar/gkx831.
• [6] In vitro identification of nonalcoholic fatty liver disease-related protein hnRNPM.World J Gastroenterol. 2015 Feb 14;21(6):1784-93. doi: 10.3748/wjg.v21.i6.1784.
• [7] Cancer-Associated MORC2-Mutant M276I Regulates an hnRNPM-Mediated CD44 Splicing Switch to Promote Invasion and Metastasis in Triple-Negative Breast Cancer.Cancer Res. 2018 Oct 15;78(20):5780-5792. doi: 10.1158/0008-5472.CAN-17-1394. Epub 2018 Aug 9.
• [8] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [9] Unusual Processing Generates SPA LncRNAs that Sequester Multiple RNA Binding Proteins.Mol Cell. 2016 Nov 3;64(3):534-548. doi: 10.1016/j.molcel.2016.10.007. Epub 2016 Oct 27.
• [10] Cell type-restricted activity of hnRNPM promotes breast cancer metastasis via regulating alternative splicing.Genes Dev. 2014 Jun 1;28(11):1191-203. doi: 10.1101/gad.241968.114. Epub 2014 May 19.
• [11] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [12] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [13] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [14] 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.
• [15] 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.
• [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] Consequences of the natural retinoid/retinoid X receptor ligands action in human breast cancer MDA-MB-231 cell line: Focus on functional proteomics. Toxicol Lett. 2017 Nov 5;281:26-34. doi: 10.1016/j.toxlet.2017.09.001. Epub 2017 Sep 5.
• [18] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [19] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [20] 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.
• [21] 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.
• [22] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [23] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [24] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [25] Genomic analysis of pterostilbene predicts its antiproliferative effects against pancreatic cancer in vitro and in vivo. J Gastrointest Surg. 2012 Jun;16(6):1136-43. doi: 10.1007/s11605-012-1869-7. Epub 2012 Mar 27.
• [26] The analysis of doxorubicin resistance in human breast cancer cells using antibody microarrays. Mol Cancer Ther. 2006 Aug;5(8):2115-20. doi: 10.1158/1535-7163.MCT-06-0190.