Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGU8TZM)

• DOT Name: Double-strand break repair protein MRE11 (MRE11)
• Synonyms: EC 3.1.-.-; Double-strand break repair protein MRE11A; Meiotic recombination 11 homolog 1; MRE11 homolog 1; Meiotic recombination 11 homolog A; MRE11 homolog A
• Gene Name: MRE11
• Related Disease:
  Ataxia-telangiectasia-like disorder 1
  Breast carcinoma
  Adenocarcinoma
  Alzheimer disease
  Breast cancer
  Breast neoplasm
  Cerebellar ataxia
  Cerebellar degeneration
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Endometrial cancer
  Epithelial ovarian cancer
  Fanconi anemia complementation group A
  Fanconi's anemia
  Gastric cancer
  Glioma
  Hepatocellular carcinoma
  Hereditary breast ovarian cancer syndrome
  leukaemia
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Lymphoma, non-Hodgkin, familial
  Myocardial infarction
  Nijmegen breakage syndrome-like disorder
  Non-hodgkin lymphoma
  Ovarian cancer
  Pancreatic cancer
  Prostate carcinoma
  Prostate neoplasm
  Squamous cell carcinoma
  Systemic lupus erythematosus
  Triple negative breast cancer
  Type-1/2 diabetes
  Carcinoma
  Prostate cancer
  Rheumatoid arthritis
  Stomach cancer
  Ataxia-telangiectasia
  Hereditary neoplastic syndrome
  Endometrial carcinoma
  Nasopharyngeal carcinoma
  Neuroblastoma
  Nijmegen breakage syndrome
  Plasma cell myeloma
  Werner syndrome
  Familial ovarian cancer
  Hereditary breast carcinoma
• UniProt ID: MRE11_HUMAN
• PDB ID: 3T1I; 8BAH; 8K00
• EC Number: 3.1.-.-
• Pfam ID: PF00149 ; PF04152
• Sequence:
  MSTADALDDENTFKILVATDIHLGFMEKDAVRGNDTFVTLDEILRLAQENEVDFILLGGD
  LFHENKPSRKTLHTCLELLRKYCMGDRPVQFEILSDQSVNFGFSKFPWVNYQDGNLNISI
  PVFSIHGNHDDPTGADALCALDILSCAGFVNHFGRSMSVEKIDISPVLLQKGSTKIALYG
  LGSIPDERLYRMFVNKKVTMLRPKEDENSWFNLFVIHQNRSKHGSTNFIPEQFLDDFIDL
  VIWGHEHECKIAPTKNEQQLFYISQPGSSVVTSLSPGEAVKKHVGLLRIKGRKMNMHKIP
  LHTVRQFFMEDIVLANHPDIFNPDNPKVTQAIQSFCLEKIEEMLENAERERLGNSHQPEK
  PLVRLRVDYSGGFEPFSVLRFSQKFVDRVANPKDIIHFFRHREQKEKTGEEINFGKLITK
  PSEGTTLRVEDLVKQYFQTAEKNVQLSLLTERGMGEAVQEFVDKEEKDAIEELVKYQLEK
  TQRFLKERHIDALEDKIDEEVRRFRETRQKNTNEEDDEVREAMTRARALRSQSEESASAF
  SADDLMSIDLAEQMANDSDDSISAATNKGRGRGRGRRGGRGQNSASRGGSQRGRADTGLE
  TSTRSRNSKTAVSASRNMSIIDAFKSTRQQPSRNVTTKNYSEVIEVDESDVEEDIFPTTS
  KTDQRWSSTSSSKIMSQSQVSKGVDFESSEDDDDDPFMNTSSLRRNRR
• Function: Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11. RAD50 may be required to bind DNA ends and hold them in close proximity. This could facilitate searches for short or long regions of sequence homology in the recombining DNA templates, and may also stimulate the activity of DNA ligases and/or restrict the nuclease activity of MRE11 to prevent nucleolytic degradation past a given point. The complex may also be required for DNA damage signaling via activation of the ATM kinase. In telomeres the MRN complex may modulate t-loop formation.
• KEGG Pathway:
  Homologous recombi.tion (hsa03440)
  Non-homologous end-joining (hsa03450)
  Cellular senescence (hsa04218)
• Reactome Pathway:
  DNA Damage/Telomere Stress Induced Senescence (R-HSA-2559586)
  IRF3-mediated induction of type I IFN (R-HSA-3270619)
  HDR through Single Strand Annealing (SSA) (R-HSA-5685938)
  HDR through MMEJ (alt-NHEJ) (R-HSA-5685939)
  HDR through Homologous Recombination (HRR) (R-HSA-5685942)
  Sensing of DNA Double Strand Breaks (R-HSA-5693548)
  Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) (R-HSA-5693554)
  Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks (R-HSA-5693565)
  Resolution of D-loop Structures through Holliday Junction Intermediates (R-HSA-5693568)
  Nonhomologous End-Joining (NHEJ) (R-HSA-5693571)
  Homologous DNA Pairing and Strand Exchange (R-HSA-5693579)
  Processing of DNA double-strand break ends (R-HSA-5693607)
  Presynaptic phase of homologous DNA pairing and strand exchange (R-HSA-5693616)
  Regulation of TP53 Activity through Phosphorylation (R-HSA-6804756)
  G2/M DNA damage checkpoint (R-HSA-69473)
  Meiotic recombination (R-HSA-912446)
  Defective homologous recombination repair (HRR) due to BRCA1 loss of function (R-HSA-9701192)
  Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function (R-HSA-9704331)
  Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function (R-HSA-9704646)
  Impaired BRCA2 binding to RAD51 (R-HSA-9709570)
  Impaired BRCA2 binding to PALB2 (R-HSA-9709603)
  Cytosolic sensors of pathogen-associated DNA (R-HSA-1834949)

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ataxia-telangiectasia-like disorder 1	DISKHZ2U	Definitive	Autosomal recessive	[1]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[2]
Adenocarcinoma	DIS3IHTY	Strong	Genetic Variation	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast neoplasm	DISNGJLM	Strong	Genetic Variation	[5]
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[6]
Cerebellar degeneration	DISPBCM3	Strong	Genetic Variation	[7]
Colon cancer	DISVC52G	Strong	Genetic Variation	[8]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[10]
Endometrial cancer	DISW0LMR	Strong	Genetic Variation	[11]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[12]
Fanconi anemia complementation group A	DIS8PZLI	Strong	Biomarker	[13]
Fanconi's anemia	DISGW6Q8	Strong	Biomarker	[13]
Gastric cancer	DISXGOUK	Strong	Biomarker	[14]
Glioma	DIS5RPEH	Strong	Biomarker	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[16]
Hereditary breast ovarian cancer syndrome	DISWDUGU	Strong	Genetic Variation	[17]
leukaemia	DISS7D1V	Strong	Biomarker	[18]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[19]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[20]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[20]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Genetic Variation	[21]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[22]
Nijmegen breakage syndrome-like disorder	DISQF01Z	Strong	GermlineCausalMutation	[23]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Genetic Variation	[24]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[12]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[25]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[26]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[27]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[28]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[29]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[30]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[31]
Carcinoma	DISH9F1N	moderate	Genetic Variation	[32]
Prostate cancer	DISF190Y	moderate	Altered Expression	[26]
Rheumatoid arthritis	DISTSB4J	moderate	Biomarker	[33]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[34]
Ataxia-telangiectasia	DISP3EVR	Disputed	Genetic Variation	[35]
Hereditary neoplastic syndrome	DISGXLG5	Disputed	Genetic Variation	[36]
Endometrial carcinoma	DISXR5CY	Limited	Genetic Variation	[11]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[37]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[38]
Nijmegen breakage syndrome	DIS98HVL	Limited	Genetic Variation	[39]
Plasma cell myeloma	DIS0DFZ0	Limited	Altered Expression	[40]
Werner syndrome	DISZY45W	Limited	Biomarker	[41]
Familial ovarian cancer	DISGLR2C	Refuted	Autosomal dominant	[42]
Hereditary breast carcinoma	DISAEZT5	Refuted	Autosomal dominant	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Capecitabine	DMTS85L	Approved	Double-strand break repair protein MRE11 (MRE11) decreases the response to substance of Capecitabine.	[64]

18 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 Double-strand break repair protein MRE11 (MRE11).	[43]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Double-strand break repair protein MRE11 (MRE11).	[44]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Double-strand break repair protein MRE11 (MRE11).	[45]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Double-strand break repair protein MRE11 (MRE11).	[46]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Double-strand break repair protein MRE11 (MRE11).	[47]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Double-strand break repair protein MRE11 (MRE11).	[48]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Double-strand break repair protein MRE11 (MRE11).	[49]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Double-strand break repair protein MRE11 (MRE11).	[50]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Double-strand break repair protein MRE11 (MRE11).	[51]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Double-strand break repair protein MRE11 (MRE11).	[53]
Pentamidine	DMHZJCG	Approved	Pentamidine decreases the activity of Double-strand break repair protein MRE11 (MRE11).	[54]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Double-strand break repair protein MRE11 (MRE11).	[55]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin decreases the expression of Double-strand break repair protein MRE11 (MRE11).	[56]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Double-strand break repair protein MRE11 (MRE11).	[58]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Double-strand break repair protein MRE11 (MRE11).	[60]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Double-strand break repair protein MRE11 (MRE11).	[61]
OXYBENZONE	DMMZYX6	Investigative	OXYBENZONE increases the expression of Double-strand break repair protein MRE11 (MRE11).	[62]
Dimethylformamide	DML6O4N	Investigative	Dimethylformamide increases the expression of Double-strand break repair protein MRE11 (MRE11).	[63]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine affects the localization of Double-strand break repair protein MRE11 (MRE11).	[52]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Double-strand break repair protein MRE11 (MRE11).	[57]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Double-strand break repair protein MRE11 (MRE11).	[59]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Double-strand break repair protein MRE11 (MRE11).	[59]

References

• [1] The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. Cell. 1999 Dec 10;99(6):577-87. doi: 10.1016/s0092-8674(00)81547-0.
• [2] Inhibition of PTEN activates bovine non-growing follicles in vitro but increases DNA damage and reduces DNA repair response.Hum Reprod. 2019 Feb 1;34(2):297-307. doi: 10.1093/humrep/dey354.
• [3] Reversible mislocalization of a disease-associated MRE11 splice variant product.Sci Rep. 2018 Jul 4;8(1):10121. doi: 10.1038/s41598-018-28370-5.
• [4] Deficiency of the Mre11 DNA repair complex in Alzheimer's disease brains.Brain Res Mol Brain Res. 2004 Sep 10;128(1):1-7. doi: 10.1016/j.molbrainres.2004.05.023.
• [5] Breast cancer risk is associated with the genes encoding the DNA double-strand break repair Mre11/Rad50/Nbs1 complex.Cancer Epidemiol Biomarkers Prev. 2007 Oct;16(10):2024-32. doi: 10.1158/1055-9965.EPI-07-0116.
• [6] Exome sequencing reveals a novel MRE11 mutation in a patient with progressive myoclonic ataxia.J Neurol Sci. 2014 Feb 15;337(1-2):219-23. doi: 10.1016/j.jns.2013.11.032. Epub 2013 Dec 1.
• [7] Disease-associated MRE11 mutants impact ATM/ATR DNA damage signaling by distinct mechanisms.Hum Mol Genet. 2013 Dec 20;22(25):5146-59. doi: 10.1093/hmg/ddt368. Epub 2013 Aug 2.
• [8] A mutant allele of MRE11 found in mismatch repair-deficient tumor cells suppresses the cellular response to DNA replication fork stress in a dominant negative manner.Mol Biol Cell. 2008 Apr;19(4):1693-705. doi: 10.1091/mbc.e07-09-0975. Epub 2008 Feb 6.
• [9] MRN (MRE11-RAD50-NBS1) Complex in Human Cancer and Prognostic Implications in Colorectal Cancer.Int J Mol Sci. 2019 Feb 14;20(4):816. doi: 10.3390/ijms20040816.
• [10] RAD50/MRE11/NBS1 proteins in relation to tumour development and prognosis in patients with microsatellite stable colorectal cancer.Histol Histopathol. 2008 Dec;23(12):1495-502. doi: 10.14670/HH-23.1495.
• [11] Loss of MDC1 in Endometrial Carcinoma Is Associated With Loss of MRN Complex and MMR Deficiency.Anticancer Res. 2019 Dec;39(12):6547-6553. doi: 10.21873/anticanres.13870.
• [12] Lack of MRE11-RAD50-NBS1 (MRN) complex detection occurs frequently in low-grade epithelial ovarian cancer.BMC Cancer. 2017 Jan 10;17(1):44. doi: 10.1186/s12885-016-3026-2.
• [13] MRE11-RAD50-NBS1 promotes Fanconi Anemia R-loop suppression at transcription-replication conflicts.Nat Commun. 2019 Sep 19;10(1):4265. doi: 10.1038/s41467-019-12271-w.
• [14] Loss of BRCA1 expression leads to worse survival in patients with gastric carcinoma.World J Gastroenterol. 2013 Mar 28;19(12):1968-74. doi: 10.3748/wjg.v19.i12.1968.
• [15] SMAD3 silencing enhances DNA damage in radiation therapy by interacting with MRE11-RAD50-NBS1 complex in glioma.J Biochem. 2019 Apr 1;165(4):317-322. doi: 10.1093/jb/mvy110.
• [16] Genes associated with recurrence of hepatocellular carcinoma: integrated analysis by gene expression and methylation profiling.J Korean Med Sci. 2011 Nov;26(11):1428-38. doi: 10.3346/jkms.2011.26.11.1428. Epub 2011 Oct 27.
• [17] Prioritizing Variants in Complete Hereditary Breast and Ovarian Cancer Genes in Patients Lacking Known BRCA Mutations.Hum Mutat. 2016 Jul;37(7):640-52. doi: 10.1002/humu.22972. Epub 2016 Mar 18.
• [18] Germline variants in MRE11/RAD50/NBN complex genes in childhood leukemia.BMC Cancer. 2013 Oct 5;13:457. doi: 10.1186/1471-2407-13-457.
• [19] c-Myc targeted regulators of cell metabolism in a transgenic mouse model of papillary lung adenocarcinoma.Oncotarget. 2016 Oct 4;7(40):65514-65539. doi: 10.18632/oncotarget.11804.
• [20] Potentially functional polymorphisms in DNA repair genes and non-small-cell lung cancer survival: a pathway-based analysis.Mol Carcinog. 2012 Jul;51(7):546-52. doi: 10.1002/mc.20819. Epub 2011 Jul 7.
• [21] Genetic variation in the NBS1, MRE11, RAD50 and BLM genes and susceptibility to non-Hodgkin lymphoma.BMC Med Genet. 2009 Nov 16;10:117. doi: 10.1186/1471-2350-10-117.
• [22] MRE11A Polymorphisms Are Associated With Subclinical Atherosclerosis and Cardiovascular Risk Factors. A Case-Control Study of the GEA Mexican Project.Front Genet. 2019 May 31;10:530. doi: 10.3389/fgene.2019.00530. eCollection 2019.
• [23] Two unrelated patients with MRE11A mutations and Nijmegen breakage syndrome-like severe microcephaly.DNA Repair (Amst). 2011 Mar 7;10(3):314-21. doi: 10.1016/j.dnarep.2010.12.002. Epub 2011 Jan 12.
• [24] Genetic variation in DNA repair pathways and risk of non-Hodgkin's lymphoma.PLoS One. 2014 Jul 10;9(7):e101685. doi: 10.1371/journal.pone.0101685. eCollection 2014.
• [25] Does tumorigenesis select for or against mutations of the DNA repair-associated genes BRCA2 and MRE11?: considerations from somatic mutations in microsatellite unstable (MSI) gastrointestinal cancers.BMC Genet. 2006 Jan 17;7:3. doi: 10.1186/1471-2156-7-3.
• [26] Elevated MRE11 expression associated with progression and poor outcome in prostate cancer.J Cancer. 2019 Jul 10;10(18):4333-4340. doi: 10.7150/jca.31454. eCollection 2019.
• [27] The long tail of oncogenic drivers in prostate cancer.Nat Genet. 2018 May;50(5):645-651. doi: 10.1038/s41588-018-0078-z. Epub 2018 Apr 2.
• [28] No additional prognostic value for MRE11 in squamous cell carcinomas of the anus treated with chemo-radiotherapy.Br J Cancer. 2018 Jan;118(2):e1. doi: 10.1038/bjc.2017.410. Epub 2018 Jan 11.
• [29] Changes in the expression of telomere maintenance genes might play a role in the pathogenesis of systemic lupus erythematosus.Lupus. 2011 Jul;20(8):820-8. doi: 10.1177/0961203310397964.
• [30] Expression of potential biomarkers associated with homologous recombination repair in patients with ovarian or triple-negative breast cancer.Cancer Biomark. 2016;16(1):145-52. doi: 10.3233/CBM-150550.
• [31] High glucose induces the proliferation of prostatic cells via downregulating MRE11.Int J Mol Med. 2018 Jun;41(6):3105-3114. doi: 10.3892/ijmm.2018.3549. Epub 2018 Mar 7.
• [32] Microsatellite instability and mutation analysis of candidate genes in urothelial cell carcinomas of upper urinary tract.Oncogene. 2006 Mar 30;25(14):2113-8. doi: 10.1038/sj.onc.1209229.
• [33] The DNA Repair Nuclease MRE11A Functions as a Mitochondrial Protector and Prevents T Cell Pyroptosis and Tissue Inflammation.Cell Metab. 2019 Sep 3;30(3):477-492.e6. doi: 10.1016/j.cmet.2019.06.016. Epub 2019 Jul 18.
• [34] High expression of MRE11 correlates with poor prognosis in gastric carcinoma.Diagn Pathol. 2019 Jun 21;14(1):60. doi: 10.1186/s13000-019-0844-y.
• [35] Three new cases of ataxia-telangiectasia-like disorder: No impairment of the ATM pathway, but S-phase checkpoint defect.Hum Mutat. 2019 Oct;40(10):1690-1699. doi: 10.1002/humu.23773. Epub 2019 May 15.
• [36] Male breast cancer in a multi-gene panel testing cohort: insights and unexpected results.Breast Cancer Res Treat. 2017 Feb;161(3):575-586. doi: 10.1007/s10549-016-4085-4. Epub 2016 Dec 22.
• [37] Targeting Rad50 sensitizes human nasopharyngeal carcinoma cells to radiotherapy.BMC Cancer. 2016 Mar 7;16:190. doi: 10.1186/s12885-016-2190-8.
• [38] MRE11 inhibition highlights a replication stress-dependent vulnerability of MYCN-driven tumors.Cell Death Dis. 2018 Aug 30;9(9):895. doi: 10.1038/s41419-018-0924-z.
• [39] Contribution of Double-strand Break Repair Gene Nijmegen Breakage Syndrome 1 Genotypes, Gender Difference and Smoking Status to Taiwanese Lung Cancer.Anticancer Res. 2017 May;37(5):2417-2423. doi: 10.21873/anticanres.11581.
• [40] Differential Expression of Non-Shelterin Genes Associated with High Telomerase Levels and Telomere Shortening in Plasma Cell Disorders.PLoS One. 2015 Sep 14;10(9):e0137972. doi: 10.1371/journal.pone.0137972. eCollection 2015.
• [41] Werner syndrome protein, the MRE11 complex and ATR: menage--trois in guarding genome stability during DNA replication?.Bioessays. 2004 Mar;26(3):306-13. doi: 10.1002/bies.10411.
• [42] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [43] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [44] 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.
• [45] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [46] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [47] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [48] Deletion of NAD(P)H:quinone oxidoreductase 1 represses Mre11-Rad50-Nbs1 complex protein expression in cisplatin-induced nephrotoxicity. Toxicol Lett. 2016 Jan 22;243:22-30.
• [49] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [50] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [51] 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.
• [52] DNA methylation inhibitor 5-Aza-2'-deoxycytidine induces reversible genome-wide DNA damage that is distinctly influenced by DNA methyltransferases 1 and 3B. Mol Cell Biol. 2008 Jan;28(2):752-71. doi: 10.1128/MCB.01799-07. Epub 2007 Nov 8.
• [53] Cannabidiol-induced transcriptomic changes and cellular senescence in human Sertoli cells. Toxicol Sci. 2023 Feb 17;191(2):227-238. doi: 10.1093/toxsci/kfac131.
• [54] Bisbenzamidine derivative, pentamidine represses DNA damage response through inhibition of histone H2A acetylation. Mol Cancer. 2010 Feb 9;9:34. doi: 10.1186/1476-4598-9-34.
• [55] Resveratrol induces downregulation of DNA repair genes in MCF-7 human breast cancer cells. Eur J Cancer Prev. 2013 Jan;22(1):11-20. doi: 10.1097/CEJ.0b013e328353edcb.
• [56] Myristicin from nutmeg induces apoptosis via the mitochondrial pathway and down regulates genes of the DNA damage response pathways in human leukaemia K562 cells. Chem Biol Interact. 2014 Jul 25;218:1-9. doi: 10.1016/j.cbi.2014.04.014. Epub 2014 Apr 29.
• [57] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [58] 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.
• [59] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [60] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [61] Identification of retinoid-modulated proteins in squamous carcinoma cells using high-throughput immunoblotting. Cancer Res. 2004 Apr 1;64(7):2439-48. doi: 10.1158/0008-5472.can-03-2643.
• [62] Chromatin modifiers: A new class of pollutants with potential epigenetic effects revealed by in vitro assays and transcriptomic analyses. Toxicology. 2023 Jan 15;484:153413. doi: 10.1016/j.tox.2022.153413. Epub 2022 Dec 26.
• [63] Oxidative stress-related DNA damage and homologous recombination repairing induced by N,N-dimethylformamide. J Appl Toxicol. 2016 Jul;36(7):936-45. doi: 10.1002/jat.3226. Epub 2015 Sep 21.
• [64] Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.