Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTORRM53)

• DOT Name: Progonadoliberin-2 (GNRH2)
• Synonyms: Progonadoliberin II
• Gene Name: GNRH2
• Related Disease:
  Endometrial carcinoma
  Leiomyoma
  Pituitary gland disorder
  Prostate neoplasm
  Uterine fibroids
  Neoplasm
  Prostate cancer
  Prostate carcinoma
• UniProt ID: GON2_HUMAN
• Pfam ID: PF00446
• Sequence:
  MASSRRGLLLLLLLTAHLGPSEAQHWSHGWYPGGKRALSSAQDPQNALRPPGRALDTAAG
  SPVQTAHGLPSDALAPLDDSMPWEGRTTAQWSLHRKRHLARTLLTAAREPRPAPPSSNKV
• Function: Stimulates the secretion of gonadotropins; it stimulates the secretion of both luteinizing and follicle-stimulating hormones.
• Tissue Specificity: Midbrain; expressed at significantly higher levels outside the brain (up to 30-fold), particularly in the kidney, bone marrow and prostate.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  GnRH sig.ling pathway (hsa04912)
  GnRH secretion (hsa04929)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Hormone ligand-binding receptors (R-HSA-375281)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[1]
Leiomyoma	DISLDDFN	Strong	Altered Expression	[2]
Pituitary gland disorder	DIS7XB48	Strong	Biomarker	[3]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[4]
Uterine fibroids	DISBZRMJ	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Limited	Biomarker	[5]
Prostate cancer	DISF190Y	Limited	Altered Expression	[5]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Progonadoliberin-2 (GNRH2).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Progonadoliberin-2 (GNRH2).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Progonadoliberin-2 (GNRH2).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of Progonadoliberin-2 (GNRH2).	[9]

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 affects the methylation of Progonadoliberin-2 (GNRH2).	[10]

References

• [1] GnRH antagonists in the treatment of gynecological and breast cancers.Endocr Relat Cancer. 2003 Jun;10(2):291-9. doi: 10.1677/erc.0.0100291.
• [2] Human myometrium and leiomyomas express gonadotropin-releasing hormone 2 and gonadotropin-releasing hormone 2 receptor.Fertil Steril. 2007 Jul;88(1):39-46. doi: 10.1016/j.fertnstert.2006.11.098. Epub 2007 Feb 12.
• [3] A Type IIb, but Not Type IIa, GnRH Receptor Mediates GnRH-Induced Release of Growth Hormone in the Ricefield Eel.Front Endocrinol (Lausanne). 2018 Nov 30;9:721. doi: 10.3389/fendo.2018.00721. eCollection 2018.
• [4] Expression of GnRH type II is regulated by the androgen receptor in prostate cancer.Endocr Relat Cancer. 2007 Sep;14(3):613-24. doi: 10.1677/ERC-07-0041.
• [5] Type I gonadotropin-releasing hormone receptor mediates the antiproliferative effects of GnRH-II on prostate cancer cells.J Clin Endocrinol Metab. 2009 May;94(5):1761-7. doi: 10.1210/jc.2008-1741. Epub 2009 Feb 3.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [8] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [9] 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.
• [10] 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.