Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT60K4M0)

• DOT Name: Homeobox protein Hox-C9 (HOXC9)
• Synonyms: Homeobox protein Hox-3B
• Gene Name: HOXC9
• Related Disease:
  Bladder cancer
  Hydatidiform mole
  Neoplasm
  Neuroblastoma
  Obesity
  Urinary bladder cancer
  Urinary bladder neoplasm
  Adult glioblastoma
  Gastric cancer
  Glioblastoma multiforme
  Leukoplakia
  Lung cancer
  Lung carcinoma
  Stomach cancer
• UniProt ID: HXC9_HUMAN
• PDB ID: 2LP0; 2MSY
• Pfam ID: PF00046 ; PF04617
• Sequence:
  MSATGPISNYYVDSLISHDNEDLLASRFPATGAHPAAARPSGLVPDCSDFPSCSFAPKPA
  VFSTSWAPVPSQSSVVYHPYGPQPHLGADTRYMRTWLEPLSGAVSFPSFPAGGRHYALKP
  DAYPGRRADCGPGEGRSYPDYMYGSPGELRDRAPQTLPSPEADALAGSKHKEEKADLDPS
  NPVANWIHARSTRKKRCPYTKYQTLELEKEFLFNMYLTRDRRYEVARVLNLTERQVKIWF
  QNRRMKMKKMNKEKTDKEQS
• Function: Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Strong	Biomarker	[1]
Hydatidiform mole	DISKNP7O	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[3]
Obesity	DIS47Y1K	Strong	Biomarker	[4]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[1]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[1]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[5]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[6]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[5]
Leukoplakia	DIST3QD3	Limited	Genetic Variation	[7]
Lung cancer	DISCM4YA	Limited	Altered Expression	[5]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[5]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Homeobox protein Hox-C9 (HOXC9).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Homeobox protein Hox-C9 (HOXC9).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Homeobox protein Hox-C9 (HOXC9).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Homeobox protein Hox-C9 (HOXC9).	[11]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Homeobox protein Hox-C9 (HOXC9).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Homeobox protein Hox-C9 (HOXC9).	[14]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Homeobox protein Hox-C9 (HOXC9).	[15]

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 Homeobox protein Hox-C9 (HOXC9).	[13]

References

• [1] MiR-193a-3p promotes the multi-chemoresistance of bladder cancer by targeting the HOXC9 gene.Cancer Lett. 2015 Feb 1;357(1):105-113. doi: 10.1016/j.canlet.2014.11.002. Epub 2014 Nov 11.
• [2] The three most downstream genes of the Hox-3 cluster are expressed in human extraembryonic tissues including trophoblast of androgenetic origin.Development. 1990 Mar;108(3):471-7. doi: 10.1242/dev.108.3.471.
• [3] Histone demethylase KDM6B has an anti-tumorigenic function in neuroblastoma by promoting differentiation.Oncogenesis. 2019 Jan 4;8(1):3. doi: 10.1038/s41389-018-0112-0.
• [4] Fat depot-specific expression of HOXC9 and HOXC10 may contribute to adverse fat distribution and related metabolic traits.Obesity (Silver Spring). 2016 Jan;24(1):51-9. doi: 10.1002/oby.21317. Epub 2015 Dec 9.
• [5] Homeobox C9 suppresses Beclin1-mediated autophagy in glioblastoma by directly inhibiting the transcription of death-associated protein kinase 1.Neuro Oncol. 2016 Jun;18(6):819-29. doi: 10.1093/neuonc/nov281. Epub 2015 Nov 17.
• [6] miR-26a/HOXC9 Dysregulation Promotes Metastasis and Stem Cell-Like Phenotype of Gastric Cancer.Cell Physiol Biochem. 2018;49(4):1659-1676. doi: 10.1159/000493502. Epub 2018 Sep 11.
• [7] Chromosomal Alterations and Gene Expression Changes Associated with the Progression of Leukoplakia to Advanced Gingivobuccal Cancer.Transl Oncol. 2017 Jun;10(3):396-409. doi: 10.1016/j.tranon.2017.03.008. Epub 2017 Apr 21.
• [8] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] 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.
• [12] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [13] 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.
• [14] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [15] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.