Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB59SKB)

• DOT Name: Rhombotin-1 (LMO1)
• Synonyms: Cysteine-rich protein TTG-1; LIM domain only protein 1; LMO-1; T-cell translocation protein 1
• Gene Name: LMO1
• Related Disease:
  Acute lymphocytic leukaemia
  Childhood acute lymphoblastic leukemia
  Acute leukaemia
  Adult T-cell leukemia/lymphoma
  Advanced cancer
  Beckwith-Wiedemann syndrome
  Childhood kidney Wilms tumor
  Coeliac disease
  Colorectal carcinoma
  Hepatitis C virus infection
  Leukemia
  Lymphoblastic lymphoma
  Neoplasm
  Non-small-cell lung cancer
  Small-cell lung cancer
  Wilms tumor
  Gastric cancer
  leukaemia
  Neuroblastoma
  Patent ductus arteriosus
  Small lymphocytic lymphoma
  Stomach cancer
  Lung cancer
  Lung carcinoma
  Melanoma
  T-cell leukaemia
• UniProt ID: RBTN1_HUMAN
• Pfam ID: PF00412
• Sequence:
  MMVLDKEDGVPMLSVQPKGKQKGCAGCNRKIKDRYLLKALDKYWHEDCLKCACCDCRLGE
  VGSTLYTKANLILCRRDYLRLFGTTGNCAACSKLIPAFEMVMRARDNVYHLDCFACQLCN
  QRFCVGDKFFLKNNMILCQMDYEEGQLNGTFESQVQ
• Function: May be involved in gene regulation within neural lineage cells potentially by direct DNA binding or by binding to other transcription factors.
• Tissue Specificity: Expressed mainly in the central nervous. Low level of expression in other tissues including thymus.
• Reactome Pathway: RUNX1 regulates transcription of genes involved in differentiation of HSCs (R-HSA-8939236)

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute lymphocytic leukaemia	DISPX75S	Definitive	Genetic Variation	[1]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Definitive	Genetic Variation	[1]
Acute leukaemia	DISDQFDI	Strong	Altered Expression	[2]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Beckwith-Wiedemann syndrome	DISH15GR	Strong	Biomarker	[5]
Childhood kidney Wilms tumor	DIS0NMK3	Strong	Genetic Variation	[6]
Coeliac disease	DISIY60C	Strong	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[4]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[8]
Leukemia	DISNAKFL	Strong	Biomarker	[9]
Lymphoblastic lymphoma	DISB9ZYC	Strong	Biomarker	[10]
Neoplasm	DISZKGEW	Strong	Altered Expression	[11]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[12]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[12]
Wilms tumor	DISB6T16	Strong	Genetic Variation	[6]
Gastric cancer	DISXGOUK	moderate	Biomarker	[9]
leukaemia	DISS7D1V	moderate	Biomarker	[9]
Neuroblastoma	DISVZBI4	moderate	Genetic Variation	[13]
Patent ductus arteriosus	DIS9P8YS	moderate	Altered Expression	[14]
Small lymphocytic lymphoma	DIS30POX	moderate	Genetic Variation	[15]
Stomach cancer	DISKIJSX	moderate	Biomarker	[9]
Lung cancer	DISCM4YA	Limited	Altered Expression	[12]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[12]
Melanoma	DIS1RRCY	Limited	Genetic Variation	[16]
T-cell leukaemia	DISJ6YIF	Limited	Biomarker	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Rhombotin-1 (LMO1).	[18]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Rhombotin-1 (LMO1).	[19]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Rhombotin-1 (LMO1).	[20]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Rhombotin-1 (LMO1).	[21]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Rhombotin-1 (LMO1).	[22]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Rhombotin-1 (LMO1).	[23]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Rhombotin-1 (LMO1).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Rhombotin-1 (LMO1).	[26]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Rhombotin-1 (LMO1).	[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 Rhombotin-1 (LMO1).	[24]

References

• [1] Contributions of IKZF1, DDC, CDKN2A, CEBPE, and LMO1 Gene Polymorphisms to Acute Lymphoblastic Leukemia in a Yemeni Population.Genet Test Mol Biomarkers. 2017 Oct;21(10):592-599. doi: 10.1089/gtmb.2017.0084. Epub 2017 Aug 2.
• [2] The LMO1 and LDB1 proteins interact in human T cell acute leukaemia with the chromosomal translocation t(11;14)(p15;q11).Oncogene. 1998 Dec 17;17(24):3199-202. doi: 10.1038/sj.onc.1202353.
• [3] The LIM protein RBTN2 and the basic helix-loop-helix protein TAL1 are present in a complex in erythroid cells.Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8617-21. doi: 10.1073/pnas.91.18.8617.
• [4] LMO1 is a novel oncogene in colorectal cancer and its overexpression is a new predictive marker for anti-EGFR therapy.Tumour Biol. 2014 Aug;35(8):8161-7. doi: 10.1007/s13277-014-2066-y. Epub 2014 May 21.
• [5] Reassessment of breakpoints in chromosome 11p15.Cytogenet Cell Genet. 1993;62(1):52-3. doi: 10.1159/000133444.
• [6] LMO1 Super-Enhancer rs2168101 G>T Polymorphism Reduces Wilms Tumor Risk.J Cancer. 2019 Apr 21;10(8):1808-1813. doi: 10.7150/jca.29842. eCollection 2019.
• [7] Serum intestinal fatty acid-binding protein in the noninvasive diagnosis of celiac disease.APMIS. 2018 Mar;126(3):186-190. doi: 10.1111/apm.12800. Epub 2018 Jan 31.
• [8] Impact of soluble CD26 on treatment outcome and hepatitis C virus-specific T cells in chronic hepatitis C virus genotype 1 infection.PLoS One. 2013;8(2):e56991. doi: 10.1371/journal.pone.0056991. Epub 2013 Feb 20.
• [9] Clinical significance of LMO1 in gastric cancer tissue and its association with apoptosis of cancer cells.Oncol Lett. 2017 Dec;14(6):6511-6518. doi: 10.3892/ol.2017.7102. Epub 2017 Sep 28.
• [10] T-cell acute lymphoblastic lymphoma induced in transgenic mice by the RBTN1 and RBTN2 LIM-domain genes.Oncogene. 1992 Dec;7(12):2389-97.
• [11] LMO1 Synergizes with MYCN to Promote Neuroblastoma Initiation and Metastasis.Cancer Cell. 2017 Sep 11;32(3):310-323.e5. doi: 10.1016/j.ccell.2017.08.002. Epub 2017 Aug 31.
• [12] LMO1 functions as an oncogene by regulating TTK expression and correlates with neuroendocrine differentiation of lung cancer.Oncotarget. 2018 Jul 3;9(51):29601-29618. doi: 10.18632/oncotarget.25642. eCollection 2018 Jul 3.
• [13] LMO1 polymorphisms and the risk of neuroblastoma: Assessment of meta-analysis of case-control studies.J Cell Mol Med. 2020 Jan;24(2):1160-1168. doi: 10.1111/jcmm.14836. Epub 2019 Dec 12.
• [14] Oncogenicity of LHX2 in pancreatic ductal adenocarcinoma.Mol Biol Rep. 2014 Dec;41(12):8163-7. doi: 10.1007/s11033-014-3716-2. Epub 2014 Oct 17.
• [15] Candidate gene association analysis of acute lymphoblastic leukemia identifies new susceptibility locus at 11p15 (LMO1).Carcinogenesis. 2011 Sep;32(9):1349-53. doi: 10.1093/carcin/bgr091. Epub 2011 May 21.
• [16] Identification of cis-regulatory mutations generating de novo edges in personalized cancer gene regulatory networks.Genome Med. 2017 Aug 30;9(1):80. doi: 10.1186/s13073-017-0464-7.
• [17] The rhombotin family of cysteine-rich LIM-domain oncogenes: distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13.Proc Natl Acad Sci U S A. 1991 May 15;88(10):4367-71. doi: 10.1073/pnas.88.10.4367.
• [18] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [19] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [20] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [21] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [22] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [23] 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.
• [24] 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.
• [25] The BET bromodomain inhibitor JQ1 suppresses growth of pancreatic ductal adenocarcinoma in patient-derived xenograft models. Oncogene. 2016 Feb 18;35(7):833-45.
• [26] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [27] 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.