Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT12HDZY)

• DOT Name: Cell division cycle-associated protein 7 (CDCA7)
• Synonyms: Protein JPO1
• Gene Name: CDCA7
• Related Disease:
  Adult lymphoma
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Breast cancer
  Breast carcinoma
  Burkitt lymphoma
  Esophageal squamous cell carcinoma
  Familial prostate carcinoma
  Immunodeficiency-centromeric instability-facial anomalies syndrome 3
  Intestinal disorder
  Lung adenocarcinoma
  Lymphoid neoplasm
  Lymphoma
  Medulloblastoma
  Neoplasm
  Pediatric lymphoma
  Prostate cancer, hereditary, 1
  Retinoblastoma
  Triple negative breast cancer
  Immunodeficiency-centromeric instability-facial anomalies syndrome
  Advanced cancer
  Type-1 diabetes
• UniProt ID: CDCA7_HUMAN
• Pfam ID: PF10497
• Sequence:
  MDARRVPQKDLRVKKNLKKFRYVKLISMETSSSSDDSCDSFASDNFANTRLQSVREGCRT
  RSQCRHSGPLRVAMKFPARSTRGATNKKAESRQPSENSVTDSNSDSEDESGMNFLEKRAL
  NIKQNKAMLAKLMSELESFPGSFRGRHPLPGSDSQSRRPRRRTFPGVASRRNPERRARPL
  TRSRSRILGSLDALPMEEEEEEDKYMLVRKRKTVDGYMNEDDLPRSRRSRSSVTLPHIIR
  PVEEITEEELENVCSNSREKIYNRSLGSTCHQCRQKTIDTKTNCRNPDCWGVRGQFCGPC
  LRNRYGEEVRDALLDPNWHCPPCRGICNCSFCRQRDGRCATGVLVYLAKYHGFGNVHAYL
  KSLKQEFEMQA
• Function: Participates in MYC-mediated cell transformation and apoptosis; induces anchorage-independent growth and clonogenicity in lymphoblastoid cells. Insufficient to induce tumorigenicity when overexpressed but contributes to MYC-mediated tumorigenesis. May play a role as transcriptional regulator.
• Tissue Specificity: Ubiquitous with higher level in thymus and small intestine. Overexpressed in a large number of tumors, in blood from patients with acute myelogenous leukemia (AML) and in chronic myelogenous leukemia (CML) blast crisis.

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult lymphoma	DISK8IZR	Strong	Biomarker	[1]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Burkitt lymphoma	DIS9D5XU	Strong	Altered Expression	[4]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[5]
Familial prostate carcinoma	DISL9KNO	Strong	Biomarker	[6]
Immunodeficiency-centromeric instability-facial anomalies syndrome 3	DISA82MV	Strong	Autosomal recessive	[7]
Intestinal disorder	DISGPMUQ	Strong	Biomarker	[7]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[8]
Lymphoid neoplasm	DIS9S8BC	Strong	Altered Expression	[4]
Lymphoma	DISN6V4S	Strong	Biomarker	[1]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[9]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[1]
Prostate cancer, hereditary, 1	DISE2P4L	Strong	Biomarker	[6]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[10]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[3]
Immunodeficiency-centromeric instability-facial anomalies syndrome	DISQ0KIE	Supportive	Autosomal recessive	[7]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[3]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[11]

27 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 Cell division cycle-associated protein 7 (CDCA7).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cell division cycle-associated protein 7 (CDCA7).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cell division cycle-associated protein 7 (CDCA7).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cell division cycle-associated protein 7 (CDCA7).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cell division cycle-associated protein 7 (CDCA7).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cell division cycle-associated protein 7 (CDCA7).	[17]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cell division cycle-associated protein 7 (CDCA7).	[18]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Cell division cycle-associated protein 7 (CDCA7).	[19]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cell division cycle-associated protein 7 (CDCA7).	[19]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Cell division cycle-associated protein 7 (CDCA7).	[20]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Cell division cycle-associated protein 7 (CDCA7).	[21]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Cell division cycle-associated protein 7 (CDCA7).	[22]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Cell division cycle-associated protein 7 (CDCA7).	[23]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Cell division cycle-associated protein 7 (CDCA7).	[24]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Cell division cycle-associated protein 7 (CDCA7).	[25]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Cell division cycle-associated protein 7 (CDCA7).	[26]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Cell division cycle-associated protein 7 (CDCA7).	[27]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Cell division cycle-associated protein 7 (CDCA7).	[28]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Cell division cycle-associated protein 7 (CDCA7).	[29]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Cell division cycle-associated protein 7 (CDCA7).	[30]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Cell division cycle-associated protein 7 (CDCA7).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cell division cycle-associated protein 7 (CDCA7).	[32]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cell division cycle-associated protein 7 (CDCA7).	[33]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Cell division cycle-associated protein 7 (CDCA7).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cell division cycle-associated protein 7 (CDCA7).	[35]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cell division cycle-associated protein 7 (CDCA7).	[36]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Cell division cycle-associated protein 7 (CDCA7).	[24]

References

• [1] CDCA7 finely tunes cytoskeleton dynamics to promote lymphoma migration and invasion.Haematologica. 2020 Mar;105(3):730-740. doi: 10.3324/haematol.2018.215459. Epub 2019 Jun 20.
• [2] The Myc target gene JPO1/CDCA7 is frequently overexpressed in human tumors and has limited transforming activity in vivo.Cancer Res. 2005 Jul 1;65(13):5620-7. doi: 10.1158/0008-5472.CAN-05-0536.
• [3] Overexpression of CDCA7 predicts poor prognosis and induces EZH2-mediated progression of triple-negative breast cancer.Int J Cancer. 2018 Nov 15;143(10):2602-2613. doi: 10.1002/ijc.31766. Epub 2018 Sep 19.
• [4] CDCA7 is a critical mediator of lymphomagenesis that selectively regulates anchorage-independent growth.Haematologica. 2018 Oct;103(10):1669-1678. doi: 10.3324/haematol.2018.188961. Epub 2018 Jun 7.
• [5] Whole-Genome Sequencing Reveals Diverse Models of Structural Variations in Esophageal Squamous Cell Carcinoma.Am J Hum Genet. 2016 Feb 4;98(2):256-74. doi: 10.1016/j.ajhg.2015.12.013. Epub 2016 Jan 28.
• [6] Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.Nat Genet. 2018 Jul;50(7):928-936. doi: 10.1038/s41588-018-0142-8. Epub 2018 Jun 11.
• [7] Mutations in CDCA7 and HELLS cause immunodeficiency-centromeric instability-facial anomalies syndrome. Nat Commun. 2015 Jul 28;6:7870. doi: 10.1038/ncomms8870.
• [8] CDCA7 promotes lung adenocarcinoma proliferation via regulating the cell cycle.Pathol Res Pract. 2019 Nov;215(11):152559. doi: 10.1016/j.prp.2019.152559. Epub 2019 Aug 1.
• [9] Identification of a novel c-Myc protein interactor, JPO2, with transforming activity in medulloblastoma cells.Cancer Res. 2005 Jul 1;65(13):5607-19. doi: 10.1158/0008-5472.CAN-05-0500.
• [10] Identification of hub genes and pathways associated with retinoblastoma based on co-expression network analysis.Genet Mol Res. 2015 Dec 8;14(4):16151-61. doi: 10.4238/2015.December.8.4.
• [11] Chromosome 2q31.1 associates with ESRD in women with type 1 diabetes.J Am Soc Nephrol. 2013 Oct;24(10):1537-43. doi: 10.1681/ASN.2012111122. Epub 2013 Sep 12.
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• [19] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [20] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [21] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [22] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [23] 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.
• [24] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [25] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [26] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [27] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [28] Marked regression of liver metastasis by combined therapy of ultrasound-mediated NF kappaB-decoy transfer and transportal injection of paclitaxel, in mouse. Int J Cancer. 2008 Apr 1;122(7):1645-56. doi: 10.1002/ijc.23280.
• [29] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [30] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
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• [32] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [33] 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.
• [34] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [35] Comparative Analysis of Transcriptomic Changes including mRNA and microRNA Expression Induced by the Xenoestrogens Zearalenone and Bisphenol A in Human Ovarian Cells. Toxins (Basel). 2023 Feb 9;15(2):140. doi: 10.3390/toxins15020140.
• [36] 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.