Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT47UQZ5)

• DOT Name: LIM/homeobox protein Lhx6 (LHX6)
• Synonyms: LIM homeobox protein 6; LIM/homeobox protein Lhx6.1
• Gene Name: LHX6
• Related Disease:
  Advanced cancer
  Carcinoma
  Epithelial ovarian cancer
  Head-neck squamous cell carcinoma
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Tourette syndrome
  Breast cancer
  Breast carcinoma
  Schizophrenia
• UniProt ID: LHX6_HUMAN
• Pfam ID: PF00046 ; PF00412
• Sequence:
  MAQPGSGCKATTRCLEGTAPPAMAQSDAEALAGALDKDEGQASPCTPSTPSVCSPPSAAS
  SVPSAGKNICSSCGLEILDRYLLKVNNLIWHVRCLECSVCRTSLRQQNSCYIKNKEIFCK
  MDYFSRFGTKCARCGRQIYASDWVRRARGNAYHLACFACFSCKRQLSTGEEFGLVEEKVL
  CRIHYDTMIENLKRAAENGNGLTLEGAVPSEQDSQPKPAKRARTSFTAEQLQVMQAQFAQ
  DNNPDAQTLQKLADMTGLSRRVIQVWFQNCRARHKKHTPQHPVPPSGAPPSRLPSALSDD
  IHYTPFSSPERARMVTLHGYIESQVQCGQVHCRLPYTAPPVHLKADMDGPLSNRGEKVIL
  FQY
• Function: Probable transcription factor required for the expression of a subset of genes involved in interneurons migration and development. Functions in the specification of cortical interneuron subtypes and in the migration of GABAergic interneuron precursors from the subpallium to the cerebral cortex.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Carcinoma	DISH9F1N	Strong	Posttranslational Modification	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[1]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[3]
Lung cancer	DISCM4YA	Strong	Altered Expression	[4]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[6]
Tourette syndrome	DISX9D54	Strong	Altered Expression	[7]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[8]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[8]
Schizophrenia	DISSRV2N	No Known	Unknown	[9]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of LIM/homeobox protein Lhx6 (LHX6).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of LIM/homeobox protein Lhx6 (LHX6).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of LIM/homeobox protein Lhx6 (LHX6).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of LIM/homeobox protein Lhx6 (LHX6).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of LIM/homeobox protein Lhx6 (LHX6).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of LIM/homeobox protein Lhx6 (LHX6).	[13]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of LIM/homeobox protein Lhx6 (LHX6).	[14]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of LIM/homeobox protein Lhx6 (LHX6).	[15]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of LIM/homeobox protein Lhx6 (LHX6).	[16]
Menadione	DMSJDTY	Approved	Menadione affects the expression of LIM/homeobox protein Lhx6 (LHX6).	[16]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of LIM/homeobox protein Lhx6 (LHX6).	[17]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of LIM/homeobox protein Lhx6 (LHX6).	[20]

References

• [1] Inhibition of miR-214-3p Aids in Preventing Epithelial Ovarian Cancer Malignancy by Increasing the Expression of LHX6.Cancers (Basel). 2019 Dec 2;11(12):1917. doi: 10.3390/cancers11121917.
• [2] LHX6 is a sensitive methylation marker in head and neck carcinomas.Oncogene. 2006 Aug 17;25(36):5018-26. doi: 10.1038/sj.onc.1209509. Epub 2006 May 29.
• [3] Validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer.Oncol Rep. 2014 Feb;31(2):1014-20. doi: 10.3892/or.2013.2927. Epub 2013 Dec 16.
• [4] LHX6, An Independent Prognostic Factor, Inhibits Lung Adenocarcinoma Progression through Transcriptional Silencing of -catenin.J Cancer. 2017 Aug 2;8(13):2561-2574. doi: 10.7150/jca.19972. eCollection 2017.
• [5] Epigenetic inactivation of LHX6 mediated microcystin-LR induced hepatocarcinogenesis via the Wnt/-catenin and P53 signaling pathways.Environ Pollut. 2019 Sep;252(Pt A):216-226. doi: 10.1016/j.envpol.2019.05.049. Epub 2019 May 15.
• [6] Down-regulation of miR-214 reverses erlotinib resistance in non-small-cell lung cancer through up-regulating LHX6 expression.Sci Rep. 2017 Apr 10;7(1):781. doi: 10.1038/s41598-017-00901-6.
• [7] Evaluation of the LIM homeobox genes LHX6 and LHX8 as candidates for Tourette syndrome.Genes Brain Behav. 2012 Jun;11(4):444-51. doi: 10.1111/j.1601-183X.2012.00778.x. Epub 2012 Apr 11.
• [8] LHX6 inhibits the proliferation, invasion and migration of breast cancer cells by modulating the PI3K/Akt/mTOR signaling pathway.Eur Rev Med Pharmacol Sci. 2018 May;22(10):3067-3073. doi: 10.26355/eurrev_201805_15066.
• [9] De novo mutations in schizophrenia implicate synaptic networks. Nature. 2014 Feb 13;506(7487):179-84. doi: 10.1038/nature12929. Epub 2014 Jan 22.
• [10] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [11] 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.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [14] 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.
• [15] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [16] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [17] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [18] 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.
• [19] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [20] 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.