Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJUYU8J)

• DOT Name: Homeobox protein Hox-C8 (HOXC8)
• Synonyms: Homeobox protein Hox-3A
• Gene Name: HOXC8
• Related Disease:
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cervical cancer
  Cervical carcinoma
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Glioma
  Hepatocellular carcinoma
  Hydatidiform mole
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Triple negative breast cancer
  Bone osteosarcoma
  Carcinoma
  Matthew-Wood syndrome
  Osteosarcoma
  Pancreatic ductal carcinoma
  Advanced cancer
  Nasopharyngeal carcinoma
• UniProt ID: HXC8_HUMAN
• Pfam ID: PF00046
• Sequence:
  MSSYFVNPLFSKYKAGESLEPAYYDCRFPQSVGRSHALVYGPGGSAPGFQHASHHVQDFF
  HHGTSGISNSGYQQNPCSLSCHGDASKFYGYEALPRQSLYGAQQEASVVQYPDCKSSANT
  NSSEGQGHLNQNSSPSLMFPWMRPHAPGRRSGRQTYSRYQTLELEKEFLFNPYLTRKRRI
  EVSHALGLTERQVKIWFQNRRMKWKKENNKDKLPGARDEEKVEEEGNEEEEKEEEEKEEN
  KD
• 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.
• Reactome Pathway: Regulation of CDH11 gene transcription (R-HSA-9762293)

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[2]
Cervical cancer	DISFSHPF	Strong	Biomarker	[3]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[3]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[4]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[5]
Glioma	DIS5RPEH	Strong	Altered Expression	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[7]
Hydatidiform mole	DISKNP7O	Strong	Altered Expression	[8]
Lung cancer	DISCM4YA	Strong	Altered Expression	[9]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[9]
Neoplasm	DISZKGEW	Strong	Altered Expression	[10]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[9]
Prostate cancer	DISF190Y	Strong	Biomarker	[11]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[11]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[12]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[13]
Bone osteosarcoma	DIST1004	moderate	Biomarker	[14]
Carcinoma	DISH9F1N	moderate	Biomarker	[15]
Matthew-Wood syndrome	DISA7HR7	moderate	Altered Expression	[15]
Osteosarcoma	DISLQ7E2	moderate	Biomarker	[14]
Pancreatic ductal carcinoma	DIS26F9Q	moderate	Biomarker	[15]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[1]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Homeobox protein Hox-C8 (HOXC8).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Homeobox protein Hox-C8 (HOXC8).	[18]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Homeobox protein Hox-C8 (HOXC8).	[19]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Homeobox protein Hox-C8 (HOXC8).	[20]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Homeobox protein Hox-C8 (HOXC8).	[21]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Homeobox protein Hox-C8 (HOXC8).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Homeobox protein Hox-C8 (HOXC8).	[24]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Homeobox protein Hox-C8 (HOXC8).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Homeobox protein Hox-C8 (HOXC8).	[26]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Homeobox protein Hox-C8 (HOXC8).	[27]

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 increases the methylation of Homeobox protein Hox-C8 (HOXC8).	[23]

References

• [1] HOXC8 regulates self-renewal, differentiation and transformation of breast cancer stem cells.Mol Cancer. 2017 Feb 16;16(1):38. doi: 10.1186/s12943-017-0605-z.
• [2] HOXC8 promotes breast tumorigenesis by transcriptionally facilitating cadherin-11 expression.Oncotarget. 2014 May 15;5(9):2596-607. doi: 10.18632/oncotarget.1841.
• [3] Upregulated expression of HOXC8 is associated with poor prognosis of cervical cancer.Oncol Lett. 2018 May;15(5):7291-7296. doi: 10.3892/ol.2018.8200. Epub 2018 Mar 7.
• [4] Down-regulation of long non-coding RNA HOTAIR inhibits invasion and migration of oesophageal cancer cells via up-regulation of microRNA-204.J Cell Mol Med. 2019 Oct;23(10):6595-6610. doi: 10.1111/jcmm.14502. Epub 2019 Aug 7.
• [5] Targeting HOX/PBX dimer formation as a potential therapeutic option in esophageal squamous cell carcinoma.Cancer Sci. 2019 May;110(5):1735-1745. doi: 10.1111/cas.13993. Epub 2019 Apr 5.
• [6] Effect of rs11614913 Polymorphism on Mature miR196a2 Expression and its Target Gene HOXC8 Expression in Human Glioma.J Mol Neurosci. 2017 Feb;61(2):144-151. doi: 10.1007/s12031-016-0855-z. Epub 2016 Oct 28.
• [7] Upregulated HOXC8 Expression Is Associated with Poor Prognosis and Oxaliplatin Resistance in Hepatocellular Carcinoma.Dig Dis Sci. 2015 Nov;60(11):3351-63. doi: 10.1007/s10620-015-3774-x. Epub 2015 Jun 30.
• [8] 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.
• [9] Homeobox C8 is a transcriptional repressor of E-cadherin gene expression in non-small cell lung cancer.Int J Biochem Cell Biol. 2019 Sep;114:105557. doi: 10.1016/j.biocel.2019.06.005. Epub 2019 Jun 13.
• [10] HOXC8 promotes proliferation and migration through transcriptional up-regulation of TGF1 in non-small cell lung cancer.Oncogenesis. 2018 Jan 17;7(2):1. doi: 10.1038/s41389-017-0016-4.
• [11] HOXC8 inhibits androgen receptor signaling in human prostate cancer cells by inhibiting SRC-3 recruitment to direct androgen target genes.Mol Cancer Res. 2010 Dec;8(12):1643-55. doi: 10.1158/1541-7786.MCR-10-0111. Epub 2010 Nov 2.
• [12] PLZF regulates Pbx1 transcription and Pbx1-HoxC8 complex leads to androgen-independent prostate cancer proliferation.Prostate. 2006 Jul 1;66(10):1092-9. doi: 10.1002/pros.20443.
• [13] Upregulation of MGP by HOXC8 promotes the proliferation, migration, and EMT processes of triple-negative breast cancer.Mol Carcinog. 2019 Oct;58(10):1863-1875. doi: 10.1002/mc.23079. Epub 2019 Jul 1.
• [14] The predictive potential and oncogenic effects of HOXC8 expression on osteosarcoma.Tumour Biol. 2016 Nov;37(11):14961-14967. doi: 10.1007/s13277-016-5384-4. Epub 2016 Sep 20.
• [15] Expression of HOXC8 is inversely related to the progression and metastasis of pancreatic ductal adenocarcinoma.Br J Cancer. 2011 Jul 12;105(2):288-95. doi: 10.1038/bjc.2011.217. Epub 2011 Jun 28.
• [16] Repression of Hox genes by LMP1 in nasopharyngeal carcinoma and modulation of glycolytic pathway genes by HoxC8.Oncogene. 2015 Dec 10;34(50):6079-91. doi: 10.1038/onc.2015.53. Epub 2015 Mar 9.
• [17] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [22] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [23] 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.
• [24] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [25] 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.
• [26] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [27] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.