Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5RVUDS)

• DOT Name: Regulator of G-protein signaling 17 (RGS17)
• Synonyms: RGS17
• Gene Name: RGS17
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Lung adenocarcinoma
  Lung cancer
  Non-small-cell lung cancer
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Lung neoplasm
  Neoplasm
  Hepatocellular carcinoma
  Lung carcinoma
  Nasopharyngeal carcinoma
  Substance dependence
• UniProt ID: RGS17_HUMAN
• PDB ID: 1ZV4; 6AM3
• Pfam ID: PF00615
• Sequence:
  MRKRQQSQNEGTPAVSQAPGNQRPNNTCCFCWCCCCSCSCLTVRNEERGENAGRPTHTTK
  MESIQVLEECQNPTAEEVLSWSQNFDKMMKAPAGRNLFREFLRTEYSEENLLFWLACEDL
  KKEQNKKVIEEKARMIYEDYISILSPKEVSLDSRVREVINRNLLDPNPHMYEDAQLQIYT
  LMHRDSFPRFLNSQIYKSFVESTAGSSSES
• Function: Regulates G protein-coupled receptor signaling cascades, including signaling via muscarinic acetylcholine receptor CHRM2 and dopamine receptor DRD2. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Binds selectively to GNAZ and GNAI2 subunits, accelerates their GTPase activity and regulates their signaling activities. Negatively regulates mu-opioid receptor-mediated activation of the G-proteins.
• Tissue Specificity: Predominantly expressed in the cerebellum. Also expressed in the cortex and medulla. Weakly expressed in a number of peripheral tissues notably spleen, lung and leukocytes.
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  G alpha (z) signalling events (R-HSA-418597)
  G alpha (q) signalling events (R-HSA-416476)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[3]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[4]
Lung cancer	DISCM4YA	Strong	Biomarker	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[6]
Prostate cancer	DISF190Y	Strong	Biomarker	[1]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[1]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[7]
Lung neoplasm	DISVARNB	moderate	Altered Expression	[4]
Neoplasm	DISZKGEW	moderate	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[8]
Lung carcinoma	DISTR26C	Limited	Biomarker	[5]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[9]
Substance dependence	DISDRAAR	Limited	Genetic Variation	[10]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methamphetamine	DMPM4SK	Approved	Regulator of G-protein signaling 17 (RGS17) affects the response to substance of Methamphetamine.	[21]
Docetaxel	DMDI269	Approved	Regulator of G-protein signaling 17 (RGS17) increases the response to substance of Docetaxel.	[13]

4 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 Regulator of G-protein signaling 17 (RGS17).	[11]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Regulator of G-protein signaling 17 (RGS17).	[14]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Regulator of G-protein signaling 17 (RGS17).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Regulator of G-protein signaling 17 (RGS17).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Regulator of G-protein signaling 17 (RGS17).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Regulator of G-protein signaling 17 (RGS17).	[13]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Regulator of G-protein signaling 17 (RGS17).	[15]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Regulator of G-protein signaling 17 (RGS17).	[16]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Regulator of G-protein signaling 17 (RGS17).	[16]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Regulator of G-protein signaling 17 (RGS17).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Regulator of G-protein signaling 17 (RGS17).	[20]

References

• [1] MiR-203 inhibits the malignant behavior of prostate cancer cells by targeting RGS17.Eur Rev Med Pharmacol Sci. 2019 Jul;23(13):5667-5674. doi: 10.26355/eurrev_201907_18303.
• [2] Finding fusion genes resulting from chromosome rearrangement by analyzing the expressed sequence databases.Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13257-61. doi: 10.1073/pnas.0405490101. Epub 2004 Aug 23.
• [3] G-Protein Signaling Protein-17 (RGS17) Is Upregulated and Promotes Tumor Growth and Migration in Human Colorectal Carcinoma.Oncol Res. 2018 Jan 19;26(1):27-35. doi: 10.3727/096504017X14900515946914. Epub 2017 Mar 23.
• [4] Hsa-mir-182 suppresses lung tumorigenesis through down regulation of RGS17 expression in vitro.Biochem Biophys Res Commun. 2010 May 28;396(2):501-7. doi: 10.1016/j.bbrc.2010.04.127. Epub 2010 Apr 24.
• [5] MiRNA-199 inhibits malignant progression of lung cancer through mediating RGS17.Eur Rev Med Pharmacol Sci. 2019 Apr;23(8):3390-3400. doi: 10.26355/eurrev_201904_17703.
• [6] miR-203 inhibits cell proliferation, invasion, and migration of non-small-cell lung cancer by downregulating RGS17.Cancer Sci. 2017 Dec;108(12):2366-2372. doi: 10.1111/cas.13401. Epub 2017 Oct 12.
• [7] RGS17, an overexpressed gene in human lung and prostate cancer, induces tumor cell proliferation through the cyclic AMP-PKA-CREB pathway.Cancer Res. 2009 Mar 1;69(5):2108-16. doi: 10.1158/0008-5472.CAN-08-3495. Epub 2009 Feb 24.
• [8] MicroRNA-199 suppresses cell proliferation, migration and invasion by downregulating RGS17 in hepatocellular carcinoma.Gene. 2018 Jun 15;659:22-28. doi: 10.1016/j.gene.2018.03.053. Epub 2018 Mar 17.
• [9] RGS17 inhibits tumorigenesis and improves 5-fluorouracil sensitivity in nasopharyngeal carcinoma.Onco Targets Ther. 2018 Nov 2;11:7591-7600. doi: 10.2147/OTT.S176002. eCollection 2018.
• [10] Variation in regulator of G-protein signaling 17 gene (RGS17) is associated with multiple substance dependence diagnoses.Behav Brain Funct. 2012 May 16;8:23. doi: 10.1186/1744-9081-8-23.
• [11] 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.
• [12] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [13] Regulators of G-Protein signaling RGS10 and RGS17 regulate chemoresistance in ovarian cancer cells. Mol Cancer. 2010 Nov 2;9:289. doi: 10.1186/1476-4598-9-289.
• [14] 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.
• [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] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [17] 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.
• [18] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [19] 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.
• [20] 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.
• [21] Genome-wide association for methamphetamine dependence: convergent results from 2 samples. Arch Gen Psychiatry. 2008 Mar;65(3):345-55. doi: 10.1001/archpsyc.65.3.345.
• [22] Regulators of G-Protein signaling RGS10 and RGS17 regulate chemoresistance in ovarian cancer cells. Mol Cancer. 2010 Nov 2;9:289. doi: 10.1186/1476-4598-9-289.