Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCR4WVV)

• DOT Name: Cyclin-J (CCNJ)
• Gene Name: CCNJ
• Related Disease:
  Advanced cancer
  Bladder cancer
  Gastric cancer
  Hepatocellular carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Stomach cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Breast cancer
  Breast carcinoma
• UniProt ID: CCNJ_HUMAN
• Pfam ID: PF02984 ; PF00134
• Sequence:
  MELEGQWWRGQLAADIHQALRYKELKLPSYKGQSPQLSLRRYFADLIAIVSNRFTLCPSA
  RHLAVYLLDLFMDRYDISIQQLHLVALSCLLLASKFEEKEDSVPKLEQLNSLGCMTNMNL
  VLTKQNLLHMELLLLETFQWNLCLPTAAHFIEYYLSEAVHETDLHDGWPMICLEKTKLYM
  AKYADYFLEVSLQVAAACVASSRIILRLSPTWPTRLHRLTAYSWDFLVQCIERLLIAHDN
  DVKEANKQRGQAGPQSAQLSVFQTASQPSRPVHFQQPQYLHQTHQTSLQYRHPTSEQPSC
  QQIVSTTHTSSYTLQTCPAGFQTSVQGLGHMQTGVGMSLAIPVEVKPCLSVSYNRSYQIN
  EHYPCITPCFER

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Bladder cancer	DISUHNM0	Strong	Genetic Variation	[2]
Gastric cancer	DISXGOUK	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[4]
Stomach cancer	DISKIJSX	Strong	Biomarker	[3]
Urinary bladder cancer	DISDV4T7	Strong	Genetic Variation	[2]
Urinary bladder neoplasm	DIS7HACE	Strong	Genetic Variation	[2]
Breast cancer	DIS7DPX1	moderate	Biomarker	[5]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[5]

16 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 Cyclin-J (CCNJ).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cyclin-J (CCNJ).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cyclin-J (CCNJ).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cyclin-J (CCNJ).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cyclin-J (CCNJ).	[10]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Cyclin-J (CCNJ).	[11]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of Cyclin-J (CCNJ).	[12]
Sulindac	DM2QHZU	Approved	Sulindac decreases the expression of Cyclin-J (CCNJ).	[11]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial decreases the expression of Cyclin-J (CCNJ).	[13]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium decreases the expression of Cyclin-J (CCNJ).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Cyclin-J (CCNJ).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cyclin-J (CCNJ).	[15]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Cyclin-J (CCNJ).	[16]
Scriptaid	DM9JZ21	Preclinical	Scriptaid affects the expression of Cyclin-J (CCNJ).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Cyclin-J (CCNJ).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Cyclin-J (CCNJ).	[19]

References

• [1] CCNJ detected by triple combination array analysis as a tumor-related gene of hepatocellular carcinoma.Int J Oncol. 2015 May;46(5):1963-70. doi: 10.3892/ijo.2015.2892. Epub 2015 Feb 11.
• [2] Rs6265 polymorphism in brain-derived neurotrophic factor (Val/Val and Val/Met) promotes proliferation of bladder cancer cells by suppressing microRNA-205 and enhancing expression of cyclin J.J Cell Biochem. 2019 May;120(5):7297-7308. doi: 10.1002/jcb.28004. Epub 2018 Nov 1.
• [3] MiR-16 mediates trastuzumab and lapatinib response in ErbB-2-positive breast and gastric cancer via its novel targets CCNJ and FUBP1.Oncogene. 2016 Dec 1;35(48):6189-6202. doi: 10.1038/onc.2016.151. Epub 2016 May 9.
• [4] Up-regulation of miR-146a increases the sensitivity of non-small cell lung cancer to DDP by downregulating cyclin J.BMC Cancer. 2017 Feb 15;17(1):138. doi: 10.1186/s12885-017-3132-9.
• [5] miR-125b acts as a tumor suppressor in breast tumorigenesis via its novel direct targets ENPEP, CK2-, CCNJ, and MEGF9.PLoS One. 2013 Oct 3;8(10):e76247. doi: 10.1371/journal.pone.0076247. eCollection 2013.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [9] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [11] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [12] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [13] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
• [14] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [15] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [16] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [17] Histone deacetylase inhibitor scriptaid induces cell cycle arrest and epigenetic change in colon cancer cells. Int J Oncol. 2008 Oct;33(4):767-76.
• [18] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [19] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.