Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ4GVR1)

• DOT Name: Homeobox protein Hox-D9 (HOXD9)
• Synonyms: Homeobox protein Hox-4C; Homeobox protein Hox-5.2
• Gene Name: HOXD9
• Related Disease:
  Colorectal carcinoma
  Gastric cancer
  Mucinous adenocarcinoma
  Ovarian cancer
  Ovarian neoplasm
  Stomach cancer
  Advanced cancer
  Astrocytoma
  Cervical cancer
  Cervical carcinoma
  Cholangiocarcinoma
  Colorectal neoplasm
  Congenital contractural arachnodactyly
  Gallbladder disease
  Glioblastoma multiforme
  Glioma
  Malignant thymoma
  Neoplasm
  Osteoarthritis
  Rheumatoid arthritis
  Squamous cell carcinoma
  Hepatocellular carcinoma
  Neuroblastoma
• UniProt ID: HXD9_HUMAN
• Pfam ID: PF00046 ; PF04617
• Sequence:
  MLGGSAGRLKMSSSGTLSNYYVDSLIGHEGDEVFAARFGPPGPGAQGRPAGVADGPAATA
  AEFASCSFAPRSAVFSASWSAVPSQPPAAAAMSGLYHPYVPPPPLAASASEPGRYVRSWM
  EPLPGFPGGAGGGGGGGGGGPGRGPSPGPSGPANGRHYGIKPETRAAPAPATAASTTSSS
  STSLSSSSKRTECSVARESQGSSGPEFSCNSFLQEKAAAATGGTGPGAGIGAATGTGGSS
  EPSACSDHPIPGCSLKEEEKQHSQPQQQQLDPNNPAANWIHARSTRKKRCPYTKYQTLEL
  EKEFLFNMYLTRDRRYEVARILNLTERQVKIWFQNRRMKMKKMSKEKCPKGD
• 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

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[1]
Gastric cancer	DISXGOUK	Definitive	Biomarker	[2]
Mucinous adenocarcinoma	DISKNFE8	Definitive	Biomarker	[1]
Ovarian cancer	DISZJHAP	Definitive	Biomarker	[1]
Ovarian neoplasm	DISEAFTY	Definitive	Biomarker	[1]
Stomach cancer	DISKIJSX	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Astrocytoma	DISL3V18	Strong	Altered Expression	[4]
Cervical cancer	DISFSHPF	Strong	Biomarker	[5]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[5]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[6]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[1]
Congenital contractural arachnodactyly	DISOM1K7	Strong	Biomarker	[6]
Gallbladder disease	DISA6W3T	Strong	Altered Expression	[6]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[4]
Glioma	DIS5RPEH	Strong	Altered Expression	[7]
Malignant thymoma	DIS59MOU	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[8]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[9]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[10]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[11]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Homeobox protein Hox-D9 (HOXD9).	[13]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Homeobox protein Hox-D9 (HOXD9).	[14]

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-D9 (HOXD9).	[15]

References

• [1] Genome-wide significant risk associations for mucinous ovarian carcinoma.Nat Genet. 2015 Aug;47(8):888-97. doi: 10.1038/ng.3336. Epub 2015 Jun 15.
• [2] HOXD9 promotes the growth, invasion and metastasis of gastric cancer cells by transcriptional activation of RUFY3.J Exp Clin Cancer Res. 2019 Sep 23;38(1):412. doi: 10.1186/s13046-019-1399-1.
• [3] DNA methylation of GHSR, GNG4, HOXD9 and SALL3 is a common epigenetic alteration in thymic carcinoma.Int J Oncol. 2020 Jan;56(1):315-326. doi: 10.3892/ijo.2019.4915. Epub 2019 Nov 18.
• [4] Functional analysis of HOXD9 in human gliomas and glioma cancer stem cells.Mol Cancer. 2011 May 22;10:60. doi: 10.1186/1476-4598-10-60.
• [5] Transcription factor homeobox D9 is involved in the malignant phenotype of cervical cancer through direct binding to the human papillomavirus oncogene promoter.Gynecol Oncol. 2019 Nov;155(2):340-348. doi: 10.1016/j.ygyno.2019.08.026. Epub 2019 Aug 30.
• [6] Serum cell-free DNA methylation of OPCML and HOXD9 as a biomarker that may aid in differential diagnosis between cholangiocarcinoma and other biliary diseases.Clin Epigenetics. 2019 Mar 4;11(1):39. doi: 10.1186/s13148-019-0634-0.
• [7] 11 Long noncoding RNA UCA1 functions as miR-135a sponge to promote the epithelial to mesenchymal transition in glioma.J Cell Biochem. 2020 Mar;121(3):2447-2457. doi: 10.1002/jcb.29467. Epub 2019 Nov 3.
• [8] Potential role of HOXD9 in synoviocyte proliferation.Arthritis Rheum. 2001 May;44(5):1013-21. doi: 10.1002/1529-0131(200105)44:5<1013::AID-ANR180>3.0.CO;2-O.
• [9] Expression of HOXD9 in fibroblast-like synoviocytes from rheumatoid arthritis patients.Int J Mol Med. 2002 Jul;10(1):41-8.
• [10] Immunocytochemical detection of HoxD9 and Pbx1 homeodomain protein expression in Chinese esophageal squamous cell carcinomas.World J Gastroenterol. 2005 Mar 14;11(10):1562-6. doi: 10.3748/wjg.v11.i10.1562.
• [11] Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells initro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology. 2017 Jun;152(8):2022-2036.
• [12] Up-regulation of HOXC6, HOXD1, and HOXD8 homeobox gene expression in human neuroblastoma cells following chemical induction of differentiation.Tumour Biol. 1996;17(1):34-47. doi: 10.1159/000217965.
• [13] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [14] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [15] 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.