Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTD6HMV)

• DOT Name: Homeobox protein Hox-B2 (HOXB2)
• Synonyms: Homeobox protein Hox-2.8; Homeobox protein Hox-2H; K8
• Gene Name: HOXB2
• Related Disease:
  Bone osteosarcoma
  Lung cancer
  Lung carcinoma
  Non-small-cell lung cancer
  Osteosarcoma
  Acute lymphocytic leukaemia
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Adult glioblastoma
  Atrichia with papular lesions
  Breast cancer
  Breast carcinoma
  Campomelic dysplasia
  Cervical cancer
  Cervical carcinoma
  Esophageal squamous cell carcinoma
  Glioblastoma multiforme
  leukaemia
  Leukemia
  Lung adenocarcinoma
  Neuroblastoma
  Pancreatic cancer
  Promyelocytic leukaemia
  Renal carcinoma
  Renal cell carcinoma
  Rheumatoid arthritis
  Bladder cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Neoplasm
• UniProt ID: HXB2_HUMAN
• Pfam ID: PF00046
• Sequence:
  MNFEFEREIGFINSQPSLAECLTSFPAVLETFQTSSIKESTLIPPPPPFEQTFPSLQPGA
  STLQRPRSQKRAEDGPALPPPPPPPLPAAPPAPEFPWMKEKKSAKKPSQSATSPSPAASA
  VPASGVGSPADGLGLPEAGGGGARRLRTAYTNTQLLELEKEFHFNKYLCRPRRVEIAALL
  DLTERQVKVWFQNRRMKHKRQTQHREPPDGEPACPGALEDICDPAEEPAASPGGPSASRA
  AWEACCHPPEVVPGALSADPRPLAVRLEGAGASSPGCALRGAGGLEPGPLPEDVFSGRQD
  SPFLPDLNFFAADSCLQLSGGLSPSLQGSLDSPVPFSEEELDFFTSTLCAIDLQFP
• 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: Activation of anterior HOX genes in hindbrain development during early embryogenesis (R-HSA-5617472)

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Definitive	Biomarker	[1]
Lung cancer	DISCM4YA	Definitive	Genetic Variation	[2]
Lung carcinoma	DISTR26C	Definitive	Genetic Variation	[2]
Non-small-cell lung cancer	DIS5Y6R9	Definitive	Biomarker	[3]
Osteosarcoma	DISLQ7E2	Definitive	Biomarker	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[4]
Acute monocytic leukemia	DIS28NEL	Strong	Altered Expression	[5]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[6]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[7]
Atrichia with papular lesions	DIS80CUB	Strong	Altered Expression	[8]
Breast cancer	DIS7DPX1	Strong	Biomarker	[9]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[9]
Campomelic dysplasia	DISVTW53	Strong	Biomarker	[10]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[11]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[11]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[12]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[7]
leukaemia	DISS7D1V	Strong	Altered Expression	[4]
Leukemia	DISNAKFL	Strong	Altered Expression	[4]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[3]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[13]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[14]
Promyelocytic leukaemia	DISYGG13	Strong	Altered Expression	[8]
Renal carcinoma	DISER9XT	Strong	Genetic Variation	[15]
Renal cell carcinoma	DISQZ2X8	Strong	Genetic Variation	[15]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[14]
Bladder cancer	DISUHNM0	moderate	Biomarker	[16]
Urinary bladder cancer	DISDV4T7	moderate	Biomarker	[16]
Urinary bladder neoplasm	DIS7HACE	moderate	Biomarker	[16]
Neoplasm	DISZKGEW	Limited	Biomarker	[6]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Homeobox protein Hox-B2 (HOXB2) affects the response to substance of Topotecan.	[27]

10 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-B2 (HOXB2).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Homeobox protein Hox-B2 (HOXB2).	[18]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Homeobox protein Hox-B2 (HOXB2).	[19]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Homeobox protein Hox-B2 (HOXB2).	[20]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Homeobox protein Hox-B2 (HOXB2).	[21]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Homeobox protein Hox-B2 (HOXB2).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Homeobox protein Hox-B2 (HOXB2).	[23]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Homeobox protein Hox-B2 (HOXB2).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Homeobox protein Hox-B2 (HOXB2).	[25]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Homeobox protein Hox-B2 (HOXB2).	[26]

References

• [1] Circular RNA 0001785 regulates the pathogenesis of osteosarcoma as a ceRNA by sponging miR-1200 to upregulate HOXB2.Cell Cycle. 2019 Jun;18(11):1281-1291. doi: 10.1080/15384101.2019.1618127. Epub 2019 May 22.
• [2] Lung cancer susceptibility genetic variants modulate HOXB2 expression in the lung.Int J Dev Biol. 2018;62(11-12):857-864. doi: 10.1387/ijdb.180210yb.
• [3] HOXB2, an adverse prognostic indicator for stage I lung adenocarcinomas, promotes invasion by transcriptional regulation of metastasis-related genes in HOP-62 non-small cell lung cancer cells.Anticancer Res. 2008 Jul-Aug;28(4B):2121-7.
• [4] Expression of selected human HOX-2 genes in B/T acute lymphoid leukemia and interleukin-2/interleukin-1 beta-stimulated natural killer lymphocytes.Blood. 1992 Jul 1;80(1):185-93.
• [5] Pediatric acute myeloid leukemia with NPM1 mutations is characterized by a gene expression profile with dysregulated HOX gene expression distinct from MLL-rearranged leukemias.Leukemia. 2007 Sep;21(9):2000-9. doi: 10.1038/sj.leu.2404808. Epub 2007 Jun 28.
• [6] The role of HOXB2 and HOXB3 in acute myeloid leukemia.Biochem Biophys Res Commun. 2015 Nov 27;467(4):742-7. doi: 10.1016/j.bbrc.2015.10.071. Epub 2015 Oct 22.
• [7] Long non-coding RNA HOXB-AS1 promotes proliferation, migration and invasion of glioblastoma cells via HOXB-AS1/miR-885-3p/HOXB2 axis.Neoplasma. 2019 May 23;66(3):386-396. doi: 10.4149/neo_2018_180606N377.
• [8] Regulation of Hoxb2 by APL-associated PLZF protein.Oncogene. 2003 Jun 12;22(24):3685-97. doi: 10.1038/sj.onc.1206328.
• [9] A functional in vivo screen for regulators of tumor progression identifies HOXB2 as a regulator of tumor growth in breast cancer.Genomics. 2011 Sep;98(3):164-72. doi: 10.1016/j.ygeno.2011.05.011. Epub 2011 Jun 13.
• [10] Assignment of an autosomal sex reversal locus (SRA1) and campomelic dysplasia (CMPD1) to 17q24.3-q25.1.Nat Genet. 1993 Jun;4(2):170-4. doi: 10.1038/ng0693-170.
• [11] Increased expression of HOXB2 and HOXB13 proteins is associated with HPV infection and cervical cancer progression.Asian Pac J Cancer Prev. 2015;16(4):1349-53. doi: 10.7314/apjcp.2015.16.4.1349.
• [12] Genome-wide screening of DNA methylation associated with lymph node metastasis in esophageal squamous cell carcinoma.Oncotarget. 2017 Jun 6;8(23):37740-37750. doi: 10.18632/oncotarget.17147.
• [13] Modulation of HOX2 gene expression following differentiation of neuronal cell lines.Differentiation. 1992 Sep;51(1):39-47. doi: 10.1111/j.1432-0436.1992.tb00678.x.
• [14] Expression of HOXB2, a retinoic acid signaling target in pancreatic cancer and pancreatic intraepithelial neoplasia.Clin Cancer Res. 2005 May 1;11(9):3587-96. doi: 10.1158/1078-0432.CCR-04-1813.
• [15] HOX gene expression in normal and neoplastic human kidney.Int J Cancer. 1992 Jul 30;51(6):892-7. doi: 10.1002/ijc.2910510610.
• [16] HOXB2 is a Putative Tumour Promotor in Human Bladder Cancer.Anticancer Res. 2019 Dec;39(12):6915-6921. doi: 10.21873/anticanres.13912.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [21] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [22] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [23] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [24] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [25] 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.
• [26] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [27] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.