Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO5GHT1)

• DOT Name: Ras suppressor protein 1 (RSU1)
• Synonyms: RSP-1; Rsu-1
• Gene Name: RSU1
• Related Disease:
  Advanced cancer
  Familial adenomatous polyposis
  Glioma
  Hepatocellular carcinoma
  Neoplasm
  Osteoporosis
  Systemic lupus erythematosus
  Breast cancer
  Adult glioblastoma
  Breast carcinoma
  Glioblastoma multiforme
• UniProt ID: RSU1_HUMAN
• PDB ID: 7D2S; 7D2T; 7D2U; 7LT8; 7LT9
• Pfam ID: PF12799 ; PF13855
• Sequence:
  MSKSLKKLVEESREKNQPEVDMSDRGISNMLDVNGLFTLSHITQLVLSHNKLTMVPPNIA
  ELKNLEVLNFFNNQIEELPTQISSLQKLKHLNLGMNRLNTLPRGFGSLPALEVLDLTYNN
  LSENSLPGNFFYLTTLRALYLSDNDFEILPPDIGKLTKLQILSLRDNDLISLPKEIGELT
  QLKELHIQGNRLTVLPPELGNLDLTGQKQVFKAENNPWVTPIADQFQLGVSHVFEYIRSE
  TYKYLYGRHMQANPEPPKKNNDKSKKISRKPLAAKNR
• Function: Potentially plays a role in the Ras signal transduction pathway. Capable of suppressing v-Ras transformation in vitro.
• Reactome Pathway: Regulation of cytoskeletal remodeling and cell spreading by IPP complex components (R-HSA-446388)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Familial adenomatous polyposis	DISW53RE	Strong	Altered Expression	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Osteoporosis	DISF2JE0	Strong	Biomarker	[6]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	moderate	Biomarker	[8]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[9]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[8]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[9]

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 Ras suppressor protein 1 (RSU1).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ras suppressor protein 1 (RSU1).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ras suppressor protein 1 (RSU1).	[12]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ras suppressor protein 1 (RSU1).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ras suppressor protein 1 (RSU1).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Ras suppressor protein 1 (RSU1).	[15]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Ras suppressor protein 1 (RSU1).	[16]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Ras suppressor protein 1 (RSU1).	[17]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Ras suppressor protein 1 (RSU1).	[18]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ras suppressor protein 1 (RSU1).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ras suppressor protein 1 (RSU1).	[20]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Ras suppressor protein 1 (RSU1).	[13]

References

• [1] MicroRNA-409-5p is upregulated in breast cancer and its downregulation inhibits cancer development through downstream target of RSU1.Tumour Biol. 2017 May;39(5):1010428317701647. doi: 10.1177/1010428317701647.
• [2] APC +/- alters colonic fibroblast proteome in FAP.Oncotarget. 2011 Mar;2(3):197-208. doi: 10.18632/oncotarget.241.
• [3] Coordinated Expression of Ras Suppressor 1 (RSU-1) and Growth Differentiation Factor 15 (GDF15) Affects Glioma Cell Invasion.Cancers (Basel). 2019 Aug 13;11(8):1159. doi: 10.3390/cancers11081159.
• [4] Elimination of Ras Suppressor-1 from hepatocellular carcinoma cells hinders their in vitro metastatic properties.Anticancer Res. 2015 Mar;35(3):1509-12.
• [5] Identification of Ras suppressor-1 (RSU-1) as a potential breast cancer metastasis biomarker using a three-dimensional in vitro approach.Oncotarget. 2017 Apr 18;8(16):27364-27379. doi: 10.18632/oncotarget.16062.
• [6] Proteomic analysis of circulating monocytes in Chinese premenopausal females with extremely discordant bone mineral density.Proteomics. 2008 Oct;8(20):4259-72. doi: 10.1002/pmic.200700480.
• [7] Analysis of variable region genes encoding anti-Sm and anti-cardiolipin antibodies from a systemic lupus erythematosus patient.Immunology. 1995 Nov;86(3):487-94.
• [8] Inhibition of Breast Cancer Cell Invasion by Ras Suppressor-1 (RSU-1) Silencing Is Reversed by Growth Differentiation Factor-15 (GDF-15).Int J Mol Sci. 2019 Jan 4;20(1):163. doi: 10.3390/ijms20010163.
• [9] Identification of an alternatively spliced RNA for the Ras suppressor RSU-1 in human gliomas.J Neurooncol. 2002 Dec;60(3):201-11. doi: 10.1023/a:1021130620178.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] 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.
• [12] 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.
• [13] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [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] 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.
• [16] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [17] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [18] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [19] 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.
• [20] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.