Molecule Information

General Information of the Molecule (ID: Mol00536)

• Name: Quinone reductase 1 (NQO1) ,Homo sapiens
• Synonyms: Azoreductase; DT-diaphorase; DTD; Menadione reductase; NAD(P)H:quinone oxidoreductase 1; Phylloquinone reductase; Quinone reductase 1; QR1; DIA4; NMOR1
• Molecule Type: Protein
• Gene Name: NQO1
• Gene ID: 1728
• Location: chr16:69706996-69726668[-]
• Sequence:
  MVGRRALIVLAHSERTSFNYAMKEAAAAALKKKGWEVVESDLYAMNFNPIISRKDITGKL
  KDPANFQYPAESVLAYKEGHLSPDIVAEQKKLEAADLVIFQFPLQWFGVPAILKGWFERV
  FIGEFAYTYAAMYDKGPFRSKKAVLSITTGGSGSMYSLQGIHGDMNVILWPIQSGILHFC
  GFQVLEPQLTYSIGHTPADARIQILEGWKKRLENIWDETPLYFAPSSLFDLNFQAGFLMK
  KEVQDEEKNKKFGLSVGHHLGKSIPTDNQIKARK
• Function: The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.
• Uniprot ID: NQO1_HUMAN
• Ensembl ID: ENSG00000181019
• HGNC ID: HGNC:2874

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Arsenic trioxide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Lung cancer [1]

• Resistant Disease: Lung cancer [ICD-11: 2C25.5]
• Resistant Drug: Arsenic trioxide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Nrf2 signaling pathway; Activation; hsa05208
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: MTT Assay
• Mechanism Description: miR155 mediates arsenic trioxide resistance by activating Nrf2 and suppressing apoptosis in lung cancer cells. miR155 mediated ATO resistance by upregulating the Nrf2 signaling pathway, but downregulating cellular apoptosis in lung cancer cells.

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Ovarian cancer [2]

• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: A2780-DR cells; Ovary; Homo sapiens (Human); CVCL_EG64
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Clonogenic assay
• Mechanism Description: The Essential Role of H19 Contributing to Cisplatin Resistance by Regulating Glutathione Metabolism in High-Grade Serous Ovarian Cancer.Additionally, we verified that different H19 expression levels in HGSC tissues showed strong correlation with cancer recurrence. H19 knockdown in A2780-DR cells resulted in recovery of cisplatin sensitivity in vitro and in vivo. Quantitative proteomics analysis indicated that six NRF2-targeted proteins, including NQO1, GSR, G6PD, GCLC, GCLM and GSTP1 involved in the glutathione metabolism pathway, were reduced in H19-knockdown cells. Furthermore, H19-knockdown cells were markedly more sensitive to hydrogen-peroxide treatment and exhibited lower glutathione levels. Our results reveal a previously unknown link between H19 and glutathione metabolism in the regulation of cancer-drug resistance.

Clinical Trial Drug(s) 1 drug(s) in total

Amrubicin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Lung adenocarcinoma [3]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Sensitive Drug: Amrubicin
• Molecule Alteration: Missense mutation; p.P187S (c.559C>T)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: NCI-H69 cells; Lung; Homo sapiens (Human); CVCL_1579
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: NCI-H23 cells; Lung; Homo sapiens (Human); CVCL_1547
• In Vitro Model: PC-1 cells; Pancreas; Homo sapiens (Human); CVCL_S978
• In Vitro Model: PC-10 cells; Lung; Homo sapiens (Human); CVCL_7088
• In Vitro Model: QG56 cells; Lung; Homo sapiens (Human); CVCL_6943
• In Vitro Model: RERF-LC-MT cells; Lung; Homo sapiens (Human); CVCL_A473
• In Vitro Model: Sk-LC-6 cells; Lung; Homo sapiens (Human); CVCL_5474
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: SK-LC-2 cells; Lung; Homo sapiens (Human); CVCL_5468
• In Vitro Model: SK-LC-17 cells; Lung; Homo sapiens (Human); CVCL_5466
• In Vitro Model: SK-LC-1 cells; Lung; Homo sapiens (Human); CVCL_5458
• In Vitro Model: SBC3 cells; Bone marrow; Homo sapiens (Human); CVCL_1678
• In Vitro Model: RERF-LC-OK cells; Central nervous system; Homo sapiens (Human); CVCL_3154
• In Vitro Model: RERF-LC-MS cells; Lung; Homo sapiens (Human); CVCL_1655
• In Vitro Model: PC6 cells; Adrenal gland; Rattus norvegicus (Rat); CVCL_7091
• In Vitro Model: NCI-H417 cells; Lung; Homo sapiens (Human); CVCL_1602
• In Vitro Model: NCI-H1688 cells; Liver; Homo sapiens (Human); CVCL_1487
• In Vitro Model: DMS53 cells; Lung; Homo sapiens (Human); CVCL_1177
• In Vitro Model: ACC-LC-94 cells; Lung; Homo sapiens (Human); CVCL_7032
• In Vitro Model: ACC-LC-80 cells; Lymph node; Homo sapiens (Human); CVCL_7028
• In Vitro Model: ACC-LC-73 cells; Lung; Homo sapiens (Human); CVCL_7026
• In Vitro Model: ACC-LC-67 cells; Lymph node; Homo sapiens (Human); CVCL_7024
• In Vitro Model: ACC-LC-5 cells; Cervical lymph node; Homo sapiens (Human); CVCL_7020
• In Vitro Model: ACC-LC-48 cells; Pericardial effusion; Homo sapiens (Human); CVCL_7018
• In Vitro Model: ACC-LC-314 cells; Lung; Homo sapiens (Human); CVCL_7011
• In Vitro Model: ACC-LC-174 cells; Lung; Homo sapiens (Human); CVCL_7007
• In Vitro Model: ACC-LC-172 cells; Pericardial effusion; Homo sapiens (Human); CVCL_7005
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter 96 AQueous One assay
• Mechanism Description: The missense mutation p.P187S (c.559C>T) in gene NQO1 cause the sensitivity of Amrubicin by unusual activation of pro-survival pathway

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Lung cancer [ICD-11: 2C25]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Lung
• The Specified Disease: Lung cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.02E-66; Fold-change: 1.67E+00; Z-score: 2.21E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 4.56E-52; Fold-change: 1.85E+00; Z-score: 2.42E+00

Ovarian cancer [ICD-11: 2C73]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Ovary
• The Specified Disease: Ovarian cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.99E-05; Fold-change: 1.85E+00; Z-score: 2.27E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 3.53E-02; Fold-change: -6.59E-03; Z-score: -4.71E-03

References

• Ref 1: miR-155 mediates arsenic trioxide resistance by activating Nrf2 and suppressing apoptosis in lung cancer cells. Sci Rep. 2017 Sep 22;7(1):12155. doi: 10.1038/s41598-017-06061-x.
• Ref 2: The Essential Role of H19 Contributing to Cisplatin Resistance by Regulating Glutathione Metabolism in High-Grade Serous Ovarian Cancer. Sci Rep. 2016 May 19;6:26093. doi: 10.1038/srep26093.
• Ref 3: C609T polymorphism of NAD(P)H quinone oxidoreductase 1 as a predictive biomarker for response to amrubicinJ Thorac Oncol. 2011 Nov;6(11):1826-32. doi: 10.1097/JTO.0b013e318229137d.