Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ5H7AT)

• DOT Name: Homeobox protein Hox-D8 (HOXD8)
• Synonyms: Homeobox protein Hox-4E; Homeobox protein Hox-5.4
• Gene Name: HOXD8
• Related Disease:
  Neuroblastoma
  Advanced cancer
  Benign neoplasm
  Colorectal carcinoma
  Epithelial ovarian cancer
  Hepatocellular carcinoma
  Lung carcinoma
  Metastatic malignant neoplasm
  Neoplasm
  Non-small-cell lung cancer
  Type-1 diabetes
• UniProt ID: HXD8_HUMAN
• Pfam ID: PF00046
• Sequence:
  MSSYFVNPLYSKYKAAAAAAAAAGEAINPTYYDCHFAPEVGGRHAAAAAALQLYGNSAAG
  FPHAPPQAHAHPHPSPPPSGTGCGGREGRGQEYFHPGGGSPAAAYQAAPPPPPHPPPPPP
  PPPCGGIACHGEPAKFYGYDNLQRQPIFTTQQEAELVQYPDCKSSSGNIGEDPDHLNQSS
  SPSQMFPWMRPQAAPGRRRGRQTYSRFQTLELEKEFLFNPYLTRKRRIEVSHALALTERQ
  VKIWFQNRRMKWKKENNKDKFPVSRQEVKDGETKKEAQELEEDRAEGLTN
• 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

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neuroblastoma	DISVZBI4	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Benign neoplasm	DISDUXAD	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[4]
Lung carcinoma	DISTR26C	Strong	Biomarker	[3]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[5]
Type-1 diabetes	DIS7HLUB	moderate	Genetic Variation	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Homeobox protein Hox-D8 (HOXD8).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Homeobox protein Hox-D8 (HOXD8).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Homeobox protein Hox-D8 (HOXD8).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Homeobox protein Hox-D8 (HOXD8).	[9]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Homeobox protein Hox-D8 (HOXD8).	[10]

References

• [1] Functional dissection of HOXD cluster genes in regulation of neuroblastoma cell proliferation and differentiation.PLoS One. 2012;7(8):e40728. doi: 10.1371/journal.pone.0040728. Epub 2012 Aug 7.
• [2] Potential role of the HOXD8 transcription factor in cisplatin resistance and tumour metastasis in advanced epithelial ovarian cancer.Sci Rep. 2018 Sep 7;8(1):13483. doi: 10.1038/s41598-018-31030-3.
• [3] HOXD8 exerts a tumor-suppressing role in colorectal cancer as an apoptotic inducer.Int J Biochem Cell Biol. 2017 Jul;88:1-13. doi: 10.1016/j.biocel.2017.04.011. Epub 2017 Apr 27.
• [4] MiR-5692a promotes proliferation and inhibits apoptosis by targeting HOXD8 in hepatocellular carcinoma.J BUON. 2019 Jan-Feb;24(1):178-186.
• [5] microRNA-520a-3p inhibits proliferation and cancer stem cell phenotype by targeting HOXD8 in non-small cell lung cancer.Oncol Rep. 2016 Dec;36(6):3529-3535. doi: 10.3892/or.2016.5149. Epub 2016 Oct 5.
• [6] The HOXD8 locus (2q31) is linked to type I diabetes. Interaction with chromosome 6 and 11 disease susceptibility genes.Diabetes. 1995 Jan;44(1):132-6. doi: 10.2337/diab.44.1.132.
• [7] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 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.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] 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.