Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTNCZN6)

• DOT Name: Ribosome biogenesis regulatory protein homolog (RRS1)
• Gene Name: RRS1
• Related Disease:
  Gastric cancer
  Stomach cancer
  Thyroid gland carcinoma
  Thyroid gland papillary carcinoma
  Advanced cancer
  Attention deficit hyperactivity disorder
  Cervical cancer
  Cervical carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Huntington disease
  Lung adenocarcinoma
  Neoplasm
  Obesity
  Prostate cancer
  Prostate carcinoma
  Sleep apnea syndrome
  Breast cancer
  Breast carcinoma
  Hepatocellular carcinoma
  High blood pressure
  Hypertension, pregnancy-induced
  Familial isolated deficiency of vitamin E
  Hemochromatosis type 2
  Human papillomavirus infection
  Post-traumatic stress disorder
• UniProt ID: RRS1_HUMAN
• PDB ID: 8FKP; 8FKQ; 8FKR; 8FKS; 8FKT; 8FKU; 8FKV; 8FKW; 8FKX; 8FKY; 8FL0; 8IR1; 8IR3
• Pfam ID: PF04939
• Sequence:
  MEGQSVEELLAKAEQDEAEKLQRITVHKELELQFDLGNLLASDRNPPTGLRCAGPTPEAE
  LQALARDNTQLLINQLWQLPTERVEEAIVARLPEPTTRLPREKPLPRPRPLTRWQQFARL
  KGIRPKKKTNLVWDEVSGQWRRRWGYQRARDDTKEWLIEVPGNADPLEDQFAKRIQAKKE
  RVAKNELNRLRNLARAHKMQLPSAAGLHPTGHQSKEELGRAMQVAKVSTASVGRFQERLP
  KEKVPRGSGKKRKFQPLFGDFAAEKKNQLELLRVMNSKKPQLDVTRATNKQMREEDQEEA
  AKRRKMSQKGKRKGGRQGPGGKRKGGPPSQGGKRKGGLGGKMNSGPPGLGGKRKGGQRPG
  GKRRK
• Function: Involved in ribosomal large subunit assembly. May regulate the localization of the 5S RNP/5S ribonucleoprotein particle to the nucleolus.

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Definitive	Biomarker	[1]
Stomach cancer	DISKIJSX	Definitive	Biomarker	[1]
Thyroid gland carcinoma	DISMNGZ0	Definitive	Biomarker	[2]
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[4]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[5]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[5]
Colon cancer	DISVC52G	Strong	Biomarker	[6]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[6]
Huntington disease	DISQPLA4	Strong	Altered Expression	[7]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Obesity	DIS47Y1K	Strong	Biomarker	[9]
Prostate cancer	DISF190Y	Strong	Biomarker	[10]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[10]
Sleep apnea syndrome	DISER6KS	Strong	Genetic Variation	[11]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[12]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[12]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[13]
High blood pressure	DISY2OHH	moderate	Biomarker	[14]
Hypertension, pregnancy-induced	DISHNU25	moderate	Biomarker	[15]
Familial isolated deficiency of vitamin E	DIS53306	Limited	Biomarker	[16]
Hemochromatosis type 2	DISYM9UP	Limited	Biomarker	[17]
Human papillomavirus infection	DISX61LX	Limited	Genetic Variation	[18]
Post-traumatic stress disorder	DISHL1EY	Limited	Genetic Variation	[19]

21 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 Ribosome biogenesis regulatory protein homolog (RRS1).	[20]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ribosome biogenesis regulatory protein homolog (RRS1).	[21]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ribosome biogenesis regulatory protein homolog (RRS1).	[22]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ribosome biogenesis regulatory protein homolog (RRS1).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ribosome biogenesis regulatory protein homolog (RRS1).	[24]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ribosome biogenesis regulatory protein homolog (RRS1).	[25]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ribosome biogenesis regulatory protein homolog (RRS1).	[26]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ribosome biogenesis regulatory protein homolog (RRS1).	[27]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Ribosome biogenesis regulatory protein homolog (RRS1).	[28]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Ribosome biogenesis regulatory protein homolog (RRS1).	[29]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ribosome biogenesis regulatory protein homolog (RRS1).	[30]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Ribosome biogenesis regulatory protein homolog (RRS1).	[31]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Ribosome biogenesis regulatory protein homolog (RRS1).	[32]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ribosome biogenesis regulatory protein homolog (RRS1).	[33]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Ribosome biogenesis regulatory protein homolog (RRS1).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ribosome biogenesis regulatory protein homolog (RRS1).	[36]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ribosome biogenesis regulatory protein homolog (RRS1).	[37]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ribosome biogenesis regulatory protein homolog (RRS1).	[38]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Ribosome biogenesis regulatory protein homolog (RRS1).	[39]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Ribosome biogenesis regulatory protein homolog (RRS1).	[40]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Ribosome biogenesis regulatory protein homolog (RRS1).	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Ribosome biogenesis regulatory protein homolog (RRS1).	[34]

References

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• [2] RRS1 gene expression involved in the progression of papillary thyroid carcinoma.Cancer Cell Int. 2018 Feb 13;18:20. doi: 10.1186/s12935-018-0519-x. eCollection 2018.
• [3] Endoplasmic reticulum stress contributes to vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells.Cancer Lett. 2010 Oct 1;296(1):123-31. doi: 10.1016/j.canlet.2010.04.002.
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• [5] Up-regulation of miRNA-148a inhibits proliferation, invasion, and migration while promoting apoptosis of cervical cancer cells by down-regulating RRS1.Biosci Rep. 2019 May 7;39(5):BSR20181815. doi: 10.1042/BSR20181815. Print 2019 May 31.
• [6] RRS1 silencing suppresses colorectal cancer cell proliferation and tumorigenesis by inhibiting G2/M progression and angiogenesis.Oncotarget. 2017 Sep 15;8(47):82968-82980. doi: 10.18632/oncotarget.20897. eCollection 2017 Oct 10.
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• [12] Effect of RRS1 gene knockdown on BT549 cell line proliferation and apoptosis in breast cancer.Neoplasma. 2019 Jan 15;66(1):28-32. doi: 10.4149/neo_2018_171229N853. Epub 2018 Aug 9.
• [13] Knockdown of RRS1 by lentiviral-mediated RNAi promotes apoptosis and suppresses proliferation of human hepatocellular carcinoma cells.Oncol Rep. 2017 Oct;38(4):2166-2172. doi: 10.3892/or.2017.5906. Epub 2017 Aug 14.
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• [15] The Spectrum of Adverse Pregnancy Outcomes Based on Kidney Disease Diagnoses: A 20-Year Population Study.Am J Nephrol. 2019;49(5):400-409. doi: 10.1159/000499965. Epub 2019 Apr 12.
• [16] Impaired discrimination between stereoisomers of alpha-tocopherol in patients with familial isolated vitamin E deficiency.J Lipid Res. 1993 Feb;34(2):201-10.
• [17] Juvenile hormone and its receptor methoprene-tolerant promote ribosomal biogenesis and vitellogenesis in the Aedes aegypti mosquito.J Biol Chem. 2017 Jun 16;292(24):10306-10315. doi: 10.1074/jbc.M116.761387. Epub 2017 Apr 26.
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• [23] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [24] 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.
• [25] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [26] 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.
• [27] 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.
• [28] A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
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• [30] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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• [32] 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.
• [33] BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011 Sep 16;146(6):904-17.
• [34] 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.
• [35] Gene expression changes associated with cytotoxicity identified using cDNA arrays. Funct Integr Genomics. 2000 Sep;1(2):114-26.
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• [37] 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.
• [38] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [39] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [40] 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.
• [41] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.