Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF6MMLV)

• DOT Name: Ras-related and estrogen-regulated growth inhibitor (RERG)
• Synonyms: EC 3.6.5.2
• Gene Name: RERG
• Related Disease:
  Adenoma
  Advanced cancer
  Breast neoplasm
  Hepatocellular carcinoma
  Marinesco-Sjogren syndrome
  Nasopharyngeal carcinoma
  Neoplasm
• UniProt ID: RERG_HUMAN
• PDB ID: 2ATV
• EC Number: 3.6.5.2
• Pfam ID: PF00071
• Sequence:
  MAKSAEVKLAIFGRAGVGKSALVVRFLTKRFIWEYDPTLESTYRHQATIDDEVVSMEILD
  TAGQEDTIQREGHMRWGEGFVLVYDITDRGSFEEVLPLKNILDEIKKPKNVTLILVGNKA
  DLDHSRQVSTEEGEKLATELACAFYECSACTGEGNITEIFYELCREVRRRRMVQGKTRRR
  SSTTHVKQAINKMLTKISS
• Function: Binds GDP/GTP and possesses intrinsic GTPase activity. Has higher affinity for GDP than for GTP. In cell lines overexpression leads to a reduction in the rate of proliferation, colony formation and in tumorigenic potential.
• Tissue Specificity: Detected in heart, brain, placenta, lung, liver, skin, kidney and pancreas. Detected in estrogen receptor-positive breast-derived cell lines, but not in estrogen receptor-negative cell lines. Expression is decreased or lost in a significant proportion of primary breast tumors with poor clinical prognosis.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[3]
Marinesco-Sjogren syndrome	DISKEU0B	Strong	Biomarker	[4]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Ras-related and estrogen-regulated growth inhibitor (RERG) affects the response to substance of Fulvestrant.	[21]

14 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-related and estrogen-regulated growth inhibitor (RERG).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ras-related and estrogen-regulated growth inhibitor (RERG).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ras-related and estrogen-regulated growth inhibitor (RERG).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ras-related and estrogen-regulated growth inhibitor (RERG).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Ras-related and estrogen-regulated growth inhibitor (RERG).	[11]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Ras-related and estrogen-regulated growth inhibitor (RERG).	[12]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Ras-related and estrogen-regulated growth inhibitor (RERG).	[13]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Ras-related and estrogen-regulated growth inhibitor (RERG).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ras-related and estrogen-regulated growth inhibitor (RERG).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ras-related and estrogen-regulated growth inhibitor (RERG).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ras-related and estrogen-regulated growth inhibitor (RERG).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ras-related and estrogen-regulated growth inhibitor (RERG).	[19]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Ras-related and estrogen-regulated growth inhibitor (RERG).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Ras-related and estrogen-regulated growth inhibitor (RERG).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Ras-related and estrogen-regulated growth inhibitor (RERG).	[15]

References

• [1] Expression of CRABP1, GRP, and RERG mRNA in clinically non-functioning and functioning pituitary adenomas.J Endocrinol Invest. 2011 Sep;34(8):e214-8. doi: 10.3275/7481. Epub 2011 Jan 26.
• [2] RERG suppresses cell proliferation, migration and angiogenesis through ERK/NF-B signaling pathway in nasopharyngeal carcinoma.J Exp Clin Cancer Res. 2017 Jun 28;36(1):88. doi: 10.1186/s13046-017-0554-9.
• [3] Expression of the RERG gene is gender-dependent in hepatocellular carcinoma and regulated by histone deacetyltransferases.J Korean Med Sci. 2006 Oct;21(5):891-6. doi: 10.3346/jkms.2006.21.5.891.
• [4] Identification and validation of highly frequent CpG island hypermethylation in colorectal adenomas and carcinomas.Int J Cancer. 2011 Dec 15;129(12):2855-66. doi: 10.1002/ijc.25951. Epub 2011 Apr 1.
• [5] Inflammation and cancer.Environ Health Prev Med. 2018 Oct 20;23(1):50. doi: 10.1186/s12199-018-0740-1.
• [6] Hyper-Methylated Loci Persisting from Sessile Serrated Polyps to Serrated Cancers.Int J Mol Sci. 2017 Mar 2;18(3):535. doi: 10.3390/ijms18030535.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [11] 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.
• [12] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [13] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [14] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [15] 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.
• [16] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [17] 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.
• [18] Genome-wide gene expression profiling of low-dose, long-term exposure of human osteosarcoma cells to bisphenol A and its analogs bisphenols AF and S. Toxicol In Vitro. 2015 Aug;29(5):1060-9.
• [19] 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.
• [20] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [21] Fulvestrant induces resistance by modulating GPER and CDK6 expression: implication of methyltransferases, deacetylases and the hSWI/SNF chromatin remodelling complex. Br J Cancer. 2013 Nov 12;109(10):2751-62. doi: 10.1038/bjc.2013.583. Epub 2013 Oct 29.