Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWI65OA)

• DOT Name: Rho-related GTP-binding protein RhoJ (RHOJ)
• Synonyms: Ras-like protein family member 7B; Tc10-like GTP-binding protein
• Gene Name: RHOJ
• Related Disease:
  HER2/NEU overexpressing breast cancer
  Lung cancer
  Lung carcinoma
  Advanced cancer
  Breast cancer
  Cardiomyopathy
  Cataract
  Chromosomal disorder
  Colon cancer
  Colonic neoplasm
  Dilated cardiomyopathy 1A
  Idiopathic cardiomyopathy
  Lung adenocarcinoma
  Non-small-cell lung cancer
  Pancytopenia
  Primary cutaneous peripheral T-cell lymphoma not otherwise specified
  T-cell lymphoma
  Neoplasm
  Hepatosplenic T-cell lymphoma
  Adult lymphoma
  Breast carcinoma
  Coronary heart disease
  Lymphoma
  Pediatric lymphoma
• UniProt ID: RHOJ_HUMAN
• Pfam ID: PF00071
• Sequence:
  MNCKEGTDSSCGCRGNDEKKMLKCVVVGDGAVGKTCLLMSYANDAFPEEYVPTVFDHYAV
  TVTVGGKQHLLGLYDTAGQEDYNQLRPLSYPNTDVFLICFSVVNPASYHNVQEEWVPELK
  DCMPHVPYVLIGTQIDLRDDPKTLARLLYMKEKPLTYEHGVKLAKAIGAQCYLECSALTQ
  KGLKAVFDEAILTIFHPKKKKKRCSEGHSCCSII
• Function: Plasma membrane-associated small GTPase specifically involved in angiogenesis. Required for endothelial cell migration during vascular development via its interaction with GLUL. Elicits the formation of F-actin-rich structures, thereby regulating endothelial cell migration.
• Tissue Specificity: Specifically expressed in endothelial cells in different tissues, such as brain, heart, lung and liver.
• KEGG Pathway: Salmonella infection (hsa05132)
• Reactome Pathway: RHOJ GTPase cycle (R-HSA-9013409)

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
HER2/NEU overexpressing breast cancer	DISYKID5	Definitive	Biomarker	[1]
Lung cancer	DISCM4YA	Definitive	Biomarker	[2]
Lung carcinoma	DISTR26C	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Cardiomyopathy	DISUPZRG	Strong	Biomarker	[5]
Cataract	DISUD7SL	Strong	Biomarker	[6]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[7]
Colon cancer	DISVC52G	Strong	Biomarker	[8]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[8]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[9]
Idiopathic cardiomyopathy	DISUGBZL	Strong	Biomarker	[5]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[10]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[3]
Pancytopenia	DISVKEHV	Strong	Biomarker	[11]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	DIS5OHQF	Strong	Biomarker	[12]
T-cell lymphoma	DISSXRTQ	Strong	Genetic Variation	[13]
Neoplasm	DISZKGEW	moderate	Biomarker	[4]
Hepatosplenic T-cell lymphoma	DIS7KMY9	Disputed	Biomarker	[12]
Adult lymphoma	DISK8IZR	Limited	Biomarker	[13]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[4]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[14]
Lymphoma	DISN6V4S	Limited	Biomarker	[13]
Pediatric lymphoma	DIS51BK2	Limited	Biomarker	[13]

8 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 Rho-related GTP-binding protein RhoJ (RHOJ).	[15]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Rho-related GTP-binding protein RhoJ (RHOJ).	[17]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Rho-related GTP-binding protein RhoJ (RHOJ).	[18]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Rho-related GTP-binding protein RhoJ (RHOJ).	[18]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Rho-related GTP-binding protein RhoJ (RHOJ).	[20]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Rho-related GTP-binding protein RhoJ (RHOJ).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Rho-related GTP-binding protein RhoJ (RHOJ).	[22]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Rho-related GTP-binding protein RhoJ (RHOJ).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Rho-related GTP-binding protein RhoJ (RHOJ).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Rho-related GTP-binding protein RhoJ (RHOJ).	[19]

References

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• [2] Vaccination with FasL-/TCL plus MHSP65 induces improved anti-lung cancer immunity in mice.Int Immunopharmacol. 2018 Feb;55:306-311. doi: 10.1016/j.intimp.2017.12.029. Epub 2018 Jan 5.
• [3] A Protective Role for RHOJ in NonSmall Cell Lung Cancer Based on Integrated Bioinformatics Analysis.J Comput Biol. 2020 Jul;27(7):1092-1103. doi: 10.1089/cmb.2019.0209. Epub 2019 Oct 23.
• [4] Magnetic Resonance Imaging-Guided Drug Delivery to Breast Cancer Stem-Like Cells.Adv Healthc Mater. 2018 Nov;7(21):e1800266. doi: 10.1002/adhm.201800266. Epub 2018 Aug 26.
• [5] Comparative phenotypic assessment of cardiac pathology, physiology, and gene expression in C3H/HeJ, C57BL/6J, and B6C3F1/J mice.Toxicol Pathol. 2010 Oct;38(6):923-42. doi: 10.1177/0192623310382864.
• [6] A new locus for autosomal dominant posterior polar cataract in Moroccan Jews maps to chromosome 14q22-23.J Med Genet. 2006 Oct;43(10):e50. doi: 10.1136/jmg.2005.034876.
• [7] Isochromosome 7q: the primary cytogenetic abnormality in hepatosplenic gammadelta T cell lymphoma.Leukemia. 1997 Aug;11(8):1367-72. doi: 10.1038/sj.leu.2400742.
• [8] Global gene expression analysis of rat colon cancers induced by a food-borne carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.Carcinogenesis. 2004 Aug;25(8):1495-505. doi: 10.1093/carcin/bgh155. Epub 2004 Apr 1.
• [9] Functional networks of nucleocytoplasmic transport-related genes differentiate ischemic and dilated cardiomyopathies. A new therapeutic opportunity.PLoS One. 2014 Aug 19;9(8):e104709. doi: 10.1371/journal.pone.0104709. eCollection 2014.
• [10] Clinical Value and Prospective Pathway Signaling of MicroRNA-375 in Lung Adenocarcinoma: A Study Based on the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Bioinformatics Analysis.Med Sci Monit. 2017 May 23;23:2453-2464. doi: 10.12659/msm.901460.
• [11] Occult hepatosplenic T-gamma delta lymphoma. Value of genotypic analysis in the differential diagnosis.Virchows Arch. 1995;426(6):629-34. doi: 10.1007/BF00192119.
• [12] Fluorescence in situ hybridization study of chromosome 7 aberrations in hepatosplenic T-cell lymphoma: isochromosome 7q as a common abnormality accumulating in forms with features of cytologic progression.Genes Chromosomes Cancer. 2002 Mar;33(3):243-51. doi: 10.1002/gcc.10021.
• [13] Immunophenotypic Shifts in Primary Cutaneous T-Cell Lymphoma Suggest Antigenic Modulation: A Study of Sequential Biopsy Specimens.Am J Surg Pathol. 2017 Apr;41(4):431-445. doi: 10.1097/PAS.0000000000000786.
• [14] Dysregulation of endothelial colony-forming cell function by a negative feedback loop of circulating miR-146a and -146b in cardiovascular disease patients.PLoS One. 2017 Jul 20;12(7):e0181562. doi: 10.1371/journal.pone.0181562. eCollection 2017.
• [15] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [16] 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.
• [17] 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.
• [18] Influence of resveratrol on rheumatoid fibroblast-like synoviocytes analysed with gene chip transcription. Phytomedicine. 2013 Feb 15;20(3-4):310-8. doi: 10.1016/j.phymed.2012.09.020. Epub 2012 Nov 6.
• [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] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [21] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [22] 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.
• [23] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.