Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8NMHM6)

• DOT Name: Homeobox protein Hox-C11 (HOXC11)
• Synonyms: Homeobox protein Hox-3H
• Gene Name: HOXC11
• Related Disease:
  Breast neoplasm
  Acute myelogenous leukaemia
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Clear cell renal carcinoma
  Clubfoot
  Congenital vertical talus
  Cutaneous melanoma
  Melanoma
  Neoplasm
  Non-small-cell lung cancer
  Renal cell carcinoma
  Neuroblastoma
  Glioblastoma multiforme
• UniProt ID: HXC11_HUMAN
• Pfam ID: PF12045 ; PF00046
• Sequence:
  MFNSVNLGNFCSPSRKERGADFGERGSCASNLYLPSCTYYMPEFSTVSSFLPQAPSRQIS
  YPYSAQVPPVREVSYGLEPSGKWHHRNSYSSCYAAADELMHRECLPPSTVTEILMKNEGS
  YGGHHHPSAPHATPAGFYSSVNKNSVLPQAFDRFFDNAYCGGGDPPAEPPCSGKGEAKGE
  PEAPPASGLASRAEAGAEAEAEEENTNPSSSGSAHSVAKEPAKGAAPNAPRTRKKRCPYS
  KFQIRELEREFFFNVYINKEKRLQLSRMLNLTDRQVKIWFQNRRMKEKKLSRDRLQYFSG
  NPLL
• 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. Binds to a promoter element of the lactase-phlorizin hydrolase gene.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast neoplasm	DISNGJLM	Definitive	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[3]
Clubfoot	DISLXT4S	Strong	Genetic Variation	[4]
Congenital vertical talus	DISZF3HD	Strong	Genetic Variation	[4]
Cutaneous melanoma	DIS3MMH9	Strong	Altered Expression	[5]
Melanoma	DIS1RRCY	Strong	Altered Expression	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[6]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[3]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[7]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Homeobox protein Hox-C11 (HOXC11).	[9]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Homeobox protein Hox-C11 (HOXC11).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Homeobox protein Hox-C11 (HOXC11).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Homeobox protein Hox-C11 (HOXC11).	[13]

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 affects the methylation of Homeobox protein Hox-C11 (HOXC11).	[11]

References

• [1] Prosaposin activates the androgen receptor and potentiates resistance to endocrine treatment in breast cancer.Breast Cancer Res. 2015 Sep 4;17(1):123. doi: 10.1186/s13058-015-0636-6.
• [2] Novel NUP98-HOXC11 fusion gene resulted from a chromosomal break within exon 1 of HOXC11 in acute myeloid leukemia with t(11;12)(p15;q13).Cancer Res. 2002 Aug 15;62(16):4571-4.
• [3] Overexpression of HOXC11 homeobox gene in clear cell renal cell carcinoma induces cellular proliferation and is associated with poor prognosis.Tumour Biol. 2015 Apr;36(4):2821-9. doi: 10.1007/s13277-014-2909-6. Epub 2014 Dec 5.
• [4] Deletions of 5' HOXC genes are associated with lower extremity malformations, including clubfoot and vertical talus.J Med Genet. 2016 Apr;53(4):250-5. doi: 10.1136/jmedgenet-2015-103505. Epub 2016 Jan 4.
• [5] HOXC11-SRC-1 regulation of S100beta in cutaneous melanoma: new targets for the kinase inhibitor dasatinib.Br J Cancer. 2011 Jun 28;105(1):118-23. doi: 10.1038/bjc.2011.193. Epub 2011 Jun 7.
• [6] MicroRNA-1197 downregulation inhibits proliferation and migration in human non- small cell lung cancer cells by upregulating HOXC11.Biomed Pharmacother. 2019 Sep;117:109041. doi: 10.1016/j.biopha.2019.109041. Epub 2019 Jun 7.
• [7] HOXC6 and HOXC11 increase transcription of S100beta gene in BrdU-induced in vitro differentiation of GOTO neuroblastoma cells into Schwannian cells.J Cell Mol Med. 2007 Mar-Apr;11(2):299-306. doi: 10.1111/j.1582-4934.2007.00020.x.
• [8] A Risk Classification System With Five-Gene for Survival Prediction of Glioblastoma Patients.Front Neurol. 2019 Jul 16;10:745. doi: 10.3389/fneur.2019.00745. eCollection 2019.
• [9] 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.
• [10] Identification of novel genes associated with the response to 5-FU treatment in gastric cancer cell lines using a cDNA microarray. Cancer Lett. 2004 Oct 8;214(1):19-33.
• [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.
• [12] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.