Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW0W6NP)

• DOT Name: Ras-related protein Rab-25 (RAB25)
• Synonyms: CATX-8
• Gene Name: RAB25
• Related Disease:
  Ovarian cancer
  Ovarian neoplasm
  Triple negative breast cancer
  Advanced cancer
  Bladder cancer
  Breast cancer
  Colon cancer
  Colorectal carcinoma
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Head and neck cancer
  Head and neck carcinoma
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  Non-small-cell lung cancer
  Oral cancer
  Oropharyngeal squamous cell carcinoma
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Breast carcinoma
  Colon carcinoma
  Head-neck squamous cell carcinoma
  Neoplasm
  Adenocarcinoma
  Clear cell renal carcinoma
  Cutaneous squamous cell carcinoma
  Glioblastoma multiforme
  Invasive ductal breast carcinoma
• UniProt ID: RAB25_HUMAN
• PDB ID: 2OIL; 3TSO
• Pfam ID: PF00071
• Sequence:
  MGNGTEEDYNFVFKVVLIGESGVGKTNLLSRFTRNEFSHDSRTTIGVEFSTRTVMLGTAA
  VKAQIWDTAGLERYRAITSAYYRGAVGALLVFDLTKHQTYAVVERWLKELYDHAEATIVV
  MLVGNKSDLSQAREVPTEEARMFAENNGLLFLETSALDSTNVELAFETVLKEIFAKVSKQ
  RQNSIRTNAITLGSAQAGQEPGPGEKRACCISL
• Function: Involved in the regulation of cell survival. Promotes invasive migration of cells in which it functions to localize and maintain integrin alpha-V/beta-1 at the tips of extending pseudopodia. Involved in the regulation of epithelial morphogenesis through the control of CLDN4 expression and localization at tight junctions. May selectively regulate the apical recycling pathway. Together with MYO5B regulates transcytosis.
• Tissue Specificity: Expressed in ovarian epithelium (NOE) and breast tissue. Expressed in ovarian cancer; expression is increased relative to NOE cells. Expression in ovarian cancer is stage dependent, with stage III and stage IV showing higher levels than early stage cancers. Expressed in breast cancer; expression is increased relative to normal breast tissue.
• Reactome Pathway: RAB geranylgeranylation (R-HSA-8873719)

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ovarian cancer	DISZJHAP	Definitive	Biomarker	[1]
Ovarian neoplasm	DISEAFTY	Definitive	Biomarker	[1]
Triple negative breast cancer	DISAMG6N	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Colon cancer	DISVC52G	Strong	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[7]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[1]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[8]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[9]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[10]
Lung cancer	DISCM4YA	Strong	Biomarker	[11]
Lung carcinoma	DISTR26C	Strong	Biomarker	[11]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[12]
Oral cancer	DISLD42D	Strong	Biomarker	[9]
Oropharyngeal squamous cell carcinoma	DIS7D7QV	Strong	Altered Expression	[13]
Prostate cancer	DISF190Y	Strong	Altered Expression	[14]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[14]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[15]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[4]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[5]
Colon carcinoma	DISJYKUO	moderate	Biomarker	[6]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Altered Expression	[9]
Neoplasm	DISZKGEW	moderate	Biomarker	[16]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[17]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[15]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Altered Expression	[16]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[18]
Invasive ductal breast carcinoma	DIS43J58	Limited	Altered Expression	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Ras-related protein Rab-25 (RAB25) decreases the response to substance of Arsenic trioxide.	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Ras-related protein Rab-25 (RAB25).	[20]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Ras-related protein Rab-25 (RAB25).	[21]
Selenium	DM25CGV	Approved	Selenium increases the expression of Ras-related protein Rab-25 (RAB25).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ras-related protein Rab-25 (RAB25).	[24]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Ras-related protein Rab-25 (RAB25).	[25]

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 protein Rab-25 (RAB25).	[23]

References

• [1] Rab25 is responsible for phosphoinositide 3-kinase/AKTmediated cisplatin resistance in human epithelial ovarian cancer cells.Mol Med Rep. 2015 Mar;11(3):2173-8. doi: 10.3892/mmr.2014.2963. Epub 2014 Nov 17.
• [2] Tumor suppressor function of Rab25 in triple-negative breast cancer.Int J Cancer. 2010 Jun 15;126(12):2799-812. doi: 10.1002/ijc.24900.
• [3] Rab25 augments cancer cell invasiveness through a 1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin.Exp Mol Med. 2018 Jan 26;50(1):e435. doi: 10.1038/emm.2017.248.
• [4] Overexpression of Rab25 contributes to metastasis of bladder cancer through induction of epithelial-mesenchymal transition and activation of Akt/GSK-3/Snail signaling.Carcinogenesis. 2013 Oct;34(10):2401-8. doi: 10.1093/carcin/bgt187. Epub 2013 May 30.
• [5] MiR-577 suppresses epithelial-mesenchymal transition and metastasis of breast cancer by targeting Rab25.Thorac Cancer. 2018 Apr;9(4):472-479. doi: 10.1111/1759-7714.12612. Epub 2018 Mar 10.
• [6] Epidermal growth factor-mediated Rab25 pathway regulates integrin 1 trafficking in colon cancer.Cancer Cell Int. 2018 Mar 5;18:32. doi: 10.1186/s12935-018-0526-y. eCollection 2018.
• [7] Loss of Myosin Vb in colorectal cancer is a strong prognostic factor for disease recurrence.Br J Cancer. 2017 Nov 21;117(11):1689-1701. doi: 10.1038/bjc.2017.352. Epub 2017 Oct 12.
• [8] Rab25 is a tumor suppressor gene with antiangiogenic and anti-invasive activities in esophageal squamous cell carcinoma.Cancer Res. 2012 Nov 15;72(22):6024-35. doi: 10.1158/0008-5472.CAN-12-1269. Epub 2012 Sep 18.
• [9] Rab25 regulates invasion and metastasis in head and neck cancer.Clin Cancer Res. 2013 Mar 15;19(6):1375-88. doi: 10.1158/1078-0432.CCR-12-2858. Epub 2013 Jan 22.
• [10] Overexpression of Rab25 promotes hepatocellular carcinoma cell proliferation and invasion.Tumour Biol. 2016 Jun;37(6):7713-8. doi: 10.1007/s13277-015-4606-5. Epub 2015 Dec 21.
• [11] Suppression of Tobacco Carcinogen-Induced Lung Tumorigenesis by Aerosol-Delivered Glycerol Propoxylate Triacrylate-Spermine Copolymer/Short Hairpin Rab25 RNA Complexes in Female A/J Mice.J Aerosol Med Pulm Drug Deliv. 2017 Apr;30(2):81-90. doi: 10.1089/jamp.2016.1301. Epub 2016 Oct 28.
• [12] Expression of Ras-related protein 25 predicts chemotherapy resistance and prognosis in advanced non-small cell lung cancer.Genet Mol Res. 2015 Oct 30;14(4):13998-4008. doi: 10.4238/2015.October.29.19.
• [13] RAB25 expression is epigenetically downregulated in oral and oropharyngeal squamous cell carcinoma with lymph node metastasis.Epigenetics. 2016 Sep;11(9):653-663. doi: 10.1080/15592294.2016.1205176. Epub 2016 Jul 5.
• [14] High expression of Rab25 contributes to malignant phenotypes and biochemical recurrence in patients with prostate cancer after radical prostatectomy.Cancer Cell Int. 2017 Apr 11;17:45. doi: 10.1186/s12935-017-0411-0. eCollection 2017.
• [15] Integrative analysis reveals CRHBP inhibits renal cell carcinoma progression by regulating inflammation and apoptosis.Cancer Gene Ther. 2020 Aug;27(7-8):607-618. doi: 10.1038/s41417-019-0138-2. Epub 2019 Oct 1.
• [16] Loss of Rab25 promotes the development of skin squamous cell carcinoma through the dysregulation of integrin trafficking.J Pathol. 2019 Oct;249(2):227-240. doi: 10.1002/path.5311. Epub 2019 Jul 18.
• [17] Loss of Rab25 promotes the development of intestinal neoplasia in mice and is associated with human colorectal adenocarcinomas.J Clin Invest. 2010 Mar;120(3):840-9. doi: 10.1172/JCI40728. Epub 2010 Feb 8.
• [18] Knockdown of Ras-Related Protein 25 (Rab25) Inhibits the In Vitro Cytotoxicity and In Vivo Antitumor Activity of Human Glioblastoma Multiforme Cells.Oncol Res. 2017 Mar 13;25(3):331-340. doi: 10.3727/096504016X14736286083065.
• [19] Increased expression of Rab25 in breast cancer correlates with lymphatic metastasis.Tumour Biol. 2012 Oct;33(5):1581-7. doi: 10.1007/s13277-012-0412-5. Epub 2012 May 30.
• [20] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [21] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [22] 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.
• [23] 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.
• [24] 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.
• [25] Use of human neuroblastoma SH-SY5Y cells to evaluate glyphosate-induced effects on oxidative stress, neuronal development and cell death signaling pathways. Environ Int. 2020 Feb;135:105414. doi: 10.1016/j.envint.2019.105414. Epub 2019 Dec 23.
• [26] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.