Details of Drug Off-Target (DOT)

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

DOT Name Homeobox protein Hox-C6 (HOXC6)
Synonyms Homeobox protein CP25; Homeobox protein HHO.C8; Homeobox protein Hox-3C
Gene Name HOXC6
Related Disease
Epithelial ovarian cancer ( )
Neuroblastoma ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Acute myelogenous leukaemia ( )
Adult glioblastoma ( )
Advanced cancer ( )
Arthritis ( )
Benign prostatic hyperplasia ( )
Breast cancer ( )
Carcinoid tumor ( )
Cervical cancer ( )
Cervical carcinoma ( )
Esophageal squamous cell carcinoma ( )
Gastric cancer ( )
Glioblastoma multiforme ( )
Glioma ( )
Head-neck squamous cell carcinoma ( )
Hydatidiform mole ( )
Laryngeal carcinoma ( )
Leukemia ( )
Myeloid leukaemia ( )
Nasopharyngeal carcinoma ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Prostate neoplasm ( )
Rheumatoid arthritis ( )
Sjogren syndrome ( )
Squamous cell carcinoma ( )
Stomach cancer ( )
Triple negative breast cancer ( )
B-cell neoplasm ( )
Breast carcinoma ( )
Lymphoma, non-Hodgkin, familial ( )
Niemann-Pick disease type C ( )
Non-hodgkin lymphoma ( )
Prostate carcinoma ( )
Anaplastic large cell lymphoma ( )
Autoimmune disease ( )
Hepatocellular carcinoma ( )
Immune system disorder ( )
Prostate cancer ( )
UniProt ID
HXC6_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
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Pfam ID
PF00046
Sequence
MNSYFTNPSLSCHLAGGQDVLPNVALNSTAYDPVRHFSTYGAAVAQNRIYSTPFYSPQEN
VVFSSSRGPYDYGSNSFYQEKDMLSNCRQNTLGHNTQTSIAQDFSSEQGRTAPQDQKASI
QIYPWMQRMNSHSGVGYGADRRRGRQIYSRYQTLELEKEFHFNRYLTRRRRIEIANALCL
TERQIKIWFQNRRMKWKKESNLTSTLSGGGGGATADSLGGKEEKREETEEEKQKE
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

42 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Epithelial ovarian cancer DIS56MH2 Definitive Altered Expression [1]
Neuroblastoma DISVZBI4 Definitive Altered Expression [2]
Ovarian cancer DISZJHAP Definitive Altered Expression [1]
Ovarian neoplasm DISEAFTY Definitive Altered Expression [1]
Acute myelogenous leukaemia DISCSPTN Strong Altered Expression [3]
Adult glioblastoma DISVP4LU Strong Altered Expression [4]
Advanced cancer DISAT1Z9 Strong Altered Expression [5]
Arthritis DIST1YEL Strong Biomarker [6]
Benign prostatic hyperplasia DISI3CW2 Strong Altered Expression [7]
Breast cancer DIS7DPX1 Strong Altered Expression [8]
Carcinoid tumor DISMNRDC Strong Biomarker [9]
Cervical cancer DISFSHPF Strong Biomarker [10]
Cervical carcinoma DIST4S00 Strong Biomarker [10]
Esophageal squamous cell carcinoma DIS5N2GV Strong Biomarker [11]
Gastric cancer DISXGOUK Strong Biomarker [12]
Glioblastoma multiforme DISK8246 Strong Altered Expression [4]
Glioma DIS5RPEH Strong Altered Expression [13]
Head-neck squamous cell carcinoma DISF7P24 Strong Altered Expression [14]
Hydatidiform mole DISKNP7O Strong Altered Expression [15]
Laryngeal carcinoma DISNHCIV Strong Biomarker [16]
Leukemia DISNAKFL Strong Biomarker [3]
Myeloid leukaemia DISMN944 Strong Altered Expression [3]
Nasopharyngeal carcinoma DISAOTQ0 Strong Biomarker [17]
Neoplasm DISZKGEW Strong Biomarker [18]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [19]
Prostate neoplasm DISHDKGQ Strong Genetic Variation [20]
Rheumatoid arthritis DISTSB4J Strong Biomarker [21]
Sjogren syndrome DISUBX7H Strong Biomarker [22]
Squamous cell carcinoma DISQVIFL Strong Altered Expression [23]
Stomach cancer DISKIJSX Strong Biomarker [12]
Triple negative breast cancer DISAMG6N Strong Biomarker [24]
B-cell neoplasm DISVY326 moderate Altered Expression [25]
Breast carcinoma DIS2UE88 moderate Altered Expression [8]
Lymphoma, non-Hodgkin, familial DISCXYIZ moderate Altered Expression [25]
Niemann-Pick disease type C DIS492ZO moderate Altered Expression [26]
Non-hodgkin lymphoma DISS2Y8A moderate Altered Expression [25]
Prostate carcinoma DISMJPLE moderate Altered Expression [27]
Anaplastic large cell lymphoma DISP4D1R Limited Altered Expression [28]
Autoimmune disease DISORMTM Limited Biomarker [29]
Hepatocellular carcinoma DIS0J828 Limited Biomarker [5]
Immune system disorder DISAEGPH Limited Biomarker [29]
Prostate cancer DISF190Y Limited Altered Expression [27]
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⏷ Show the Full List of 42 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Homeobox protein Hox-C6 (HOXC6). [30]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Homeobox protein Hox-C6 (HOXC6). [31]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Homeobox protein Hox-C6 (HOXC6). [32]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Homeobox protein Hox-C6 (HOXC6). [33]
Triclosan DMZUR4N Approved Triclosan increases the expression of Homeobox protein Hox-C6 (HOXC6). [34]
Cytarabine DMZD5QR Approved Cytarabine decreases the expression of Homeobox protein Hox-C6 (HOXC6). [35]
Testosterone Undecanoate DMZO10Y Approved Testosterone Undecanoate increases the expression of Homeobox protein Hox-C6 (HOXC6). [36]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Homeobox protein Hox-C6 (HOXC6). [37]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Homeobox protein Hox-C6 (HOXC6). [38]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Homeobox protein Hox-C6 (HOXC6). [39]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of Homeobox protein Hox-C6 (HOXC6). [40]
geraniol DMS3CBD Investigative geraniol increases the expression of Homeobox protein Hox-C6 (HOXC6). [41]
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⏷ Show the Full List of 12 Drug(s)

References

1 Downregulation of HOXC6 in Serous Ovarian Cancer.Cancer Invest. 2015;33(7):303-11. doi: 10.3109/07357907.2015.1041641. Epub 2015 Jun 5.
2 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.
3 Differentiation and cell-type-restricted expression of HOXC4, HOXC5 and HOXC6 in myeloid leukemias and normal myeloid cells.Leukemia. 1998 Nov;12(11):1724-32. doi: 10.1038/sj.leu.2401106.
4 Overexpression of HOXC6 promotes cell proliferation and migration via MAPK signaling and predicts a poor prognosis in glioblastoma.Cancer Manag Res. 2019 Sep 3;11:8167-8179. doi: 10.2147/CMAR.S209904. eCollection 2019.
5 HOXC6 predicts invasion and poor survival in hepatocellular carcinoma by driving epithelial-mesenchymal transition.Aging (Albany NY). 2018 Jan 15;10(1):115-130. doi: 10.18632/aging.101363.
6 Methotrexate improves the anti-arthritic effects of Paeoniflorin-6'-O-benzene sulfonate by enhancing its pharmacokinetic properties in adjuvant-induced arthritis rats.Biomed Pharmacother. 2019 Apr;112:108644. doi: 10.1016/j.biopha.2019.108644. Epub 2019 Feb 21.
7 DNA methylation status is more reliable than gene expression at detecting cancer in prostate biopsy.Br J Cancer. 2014 Aug 12;111(4):781-9. doi: 10.1038/bjc.2014.337. Epub 2014 Jun 17.
8 Bisphenol-A induces expression of HOXC6, an estrogen-regulated homeobox-containing gene associated with breast cancer.Biochim Biophys Acta. 2015 Jun;1849(6):697-708. doi: 10.1016/j.bbagrm.2015.02.003. Epub 2015 Feb 25.
9 Hoxc6 is overexpressed in gastrointestinal carcinoids and interacts with JunD to regulate tumor growth.Gastroenterology. 2008 Sep;135(3):907-16, 916.e1-2. doi: 10.1053/j.gastro.2008.06.034. Epub 2008 Jul 23.
10 HOXC6 promotes cervical cancer progression via regulation of Bcl-2.FASEB J. 2019 Mar;33(3):3901-3911. doi: 10.1096/fj.201801099RR. Epub 2018 Dec 3.
11 Increased HOXC6 expression predicts chemotherapy sensitivity in patients with esophageal squamous cell carcinoma.Oncol Lett. 2017 Oct;14(4):4835-4840. doi: 10.3892/ol.2017.6772. Epub 2017 Aug 18.
12 HOXC6 promotes gastric cancer cell invasion by upregulating the expression of MMP9.Mol Med Rep. 2016 Oct;14(4):3261-8. doi: 10.3892/mmr.2016.5640. Epub 2016 Aug 19.
13 Knockdown of HOXC6 inhibits glioma cell proliferation and induces cell cycle arrest by targeting WIF-1 in vitro and vivo.Pathol Res Pract. 2018 Nov;214(11):1818-1824. doi: 10.1016/j.prp.2018.09.001. Epub 2018 Sep 12.
14 HOXC6 is deregulated in human head and neck squamous cell carcinoma and modulates Bcl-2 expression.J Biol Chem. 2012 Oct 12;287(42):35678-35688. doi: 10.1074/jbc.M112.361675. Epub 2012 Aug 15.
15 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.
16 Upregulation of microRNA-141 suppresses epithelial-mesenchymal transition and lymph node metastasis in laryngeal cancer through HOXC6-dependent TGF- signaling pathway.Cell Signal. 2020 Feb;66:109444. doi: 10.1016/j.cellsig.2019.109444. Epub 2019 Oct 16.
17 MicroRNA-185 inhibits cell proliferation while promoting apoptosis and autophagy through negative regulation of TGF-1/mTOR axis and HOXC6 in nasopharyngeal carcinoma.Cancer Biomark. 2018;23(1):107-123. doi: 10.3233/CBM-181459.
18 HOXC6 gene silencing inhibits epithelial-mesenchymal transition and cell viability through the TGF-/smad signaling pathway in cervical carcinoma cells.Cancer Cell Int. 2018 Dec 12;18:204. doi: 10.1186/s12935-018-0680-2. eCollection 2018.
19 Evidence for an oncogenic role of HOXC6 in human non-small cell lung cancer.PeerJ. 2019 Apr 9;7:e6629. doi: 10.7717/peerj.6629. eCollection 2019.
20 Identification of activated enhancers and linked transcription factors in breast, prostate, and kidney tumors by tracing enhancer networks using epigenetic traits.Epigenetics Chromatin. 2016 Nov 9;9:50. doi: 10.1186/s13072-016-0102-4. eCollection 2016.
21 Regulatory effects of paeoniflorin-6'-O-benzene sulfonate (CP-25) on dendritic cells maturation and activation via PGE2-EP4 signaling in adjuvant-induced arthritic rats.Inflammopharmacology. 2019 Oct;27(5):997-1010. doi: 10.1007/s10787-019-00575-8. Epub 2019 Feb 15.
22 CP-25 Alleviates Experimental Sjgren's Syndrome Features in NOD/Ltj Mice and Modulates T Lymphocyte Subsets.Basic Clin Pharmacol Toxicol. 2018 Oct;123(4):423-434. doi: 10.1111/bcpt.13025. Epub 2018 Jun 1.
23 Aberrant expression of HOX genes in oral dysplasia and squamous cell carcinoma tissues.Oncol Res. 2006;16(5):217-24. doi: 10.3727/000000006783981080.
24 Long noncoding RNA Linc00339 promotes triple-negative breast cancer progression through miR-377-3p/HOXC6 signaling pathway.J Cell Physiol. 2019 Aug;234(8):13303-13317. doi: 10.1002/jcp.28007. Epub 2019 Jan 7.
25 HOXC4, HOXC5, and HOXC6 expression in non-Hodgkin's lymphoma: preferential expression of the HOXC5 gene in primary cutaneous anaplastic T-cell and oro-gastrointestinal tract mucosa-associated B-cell lymphomas.Blood. 1997 Nov 15;90(10):4116-25.
26 HOXC6 Overexpression Is Associated With Ki-67 Expression and Poor Survival in NPC Patients.J Cancer. 2017 Jun 3;8(9):1647-1654. doi: 10.7150/jca.18893. eCollection 2017.
27 Multicenter Optimization and Validation of a 2-Gene mRNA Urine Test for Detection of Clinically Significant Prostate Cancer before Initial Prostate Biopsy.J Urol. 2019 Aug;202(2):256-263. doi: 10.1097/JU.0000000000000293. Epub 2019 Jul 8.
28 HOXC4, HOXC5, and HOXC6 expression in primary cutaneous lymphoid lesions. High expression of HOXC5 in anaplastic large-cell lymphomas.Am J Pathol. 1997 Oct;151(4):1067-74.
29 The Regulatory Effects of Paeoniflorin and Its Derivative Paeoniflorin-6'-O-Benzene Sulfonate CP-25 on Inflammation and Immune Diseases.Front Pharmacol. 2019 Feb 5;10:57. doi: 10.3389/fphar.2019.00057. eCollection 2019.
30 Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
31 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
32 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
33 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.
34 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
35 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.
36 Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
37 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
38 Gene expression profiling reveals novel regulation by bisphenol-A in estrogen receptor-alpha-positive human cells. Environ Res. 2006 Jan;100(1):86-92.
39 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
40 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
41 Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.