Molecule Information

General Information of the Molecule (ID: Mol00129)

• Name: Nuclear receptor subfamily 1 group I3 (NR1I3) ,Homo sapiens
• Synonyms: Constitutive activator of retinoid response; Constitutive active response; Constitutive androstane receptor; CAR; Orphan nuclear receptor MB67; CAR
• Molecule Type: Protein
• Gene Name: NR1I3
• Gene ID: 9970
• Location: chr1:161229666-161238244[-]
• Sequence:
  MASREDELRNCVVCGDQATGYHFNALTCEGCKGFFRRTVSKSIGPTCPFAGSCEVSKTQR
  RHCPACRLQKCLDAGMRKDMILSAEALALRRAKQAQRRAQQTPVQLSKEQEELIRTLLGA
  HTRHMGTMFEQFVQFRPPAHLFIHHQPLPTLAPVLPLVTHFADINTFMVLQVIKFTKDLP
  VFRSLPIEDQISLLKGAAVEICHIVLNTTFCLQTQNFLCGPLRYTIEDGARVSPTVGFQV
  EFLELLFHFHGTLRKLQLQEPEYVLLAAMALFSPDRPGVTQRDEIDQLQEEMALTLQSYI
  KGQQRRPRDRFLYAKLLGLLAELRSINEAYGYQIQHIQGLSAMMPLLQEICS
• Function: Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital responsive element module of the human CYP2B6 gene and the CYP3A4 xenobiotic response element.
• Uniprot ID: NR1I3_HUMAN
• Ensembl ID: ENSG00000143257
• HGNC ID: HGNC:7969

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) 1 drug(s) in total

Doxorubicin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Neuroblastoma [1]

• Sensitive Disease: Neuroblastoma [ICD-11: 2A00.11]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: UkF-NB3 cells; Bone marrow; Homo sapiens (Human); CVCL_9904
• In Vivo Model: Immunodeficient NCr nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Chromatin immunoprecipitation assay
• Experiment for Drug Resistance: Cell titer glo assay assay
• Mechanism Description: Hypermethylation of the miR-137 promoter and negative regulation of miR-137 by CAR contribute in part to reduced miR-137 expression and increased CAR and MDR1 expression in doxorubicin-resistant neuroblastoma cells.

Disease Class: Colon cancer [1]

• Sensitive Disease: Colon cancer [ICD-11: 2B90.1]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: LS174 cells; Colon; Homo sapiens (Human); CVCL_YJ85
• In Vivo Model: Immunodeficient NCr nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Chromatin immunoprecipitation assay
• Experiment for Drug Resistance: Cell titer glo assay assay
• Mechanism Description: Hypermethylation of the miR-137 promoter and negative regulation of miR-137 by CAR contribute in part to reduced miR-137 expression and increased CAR and MDR1 expression in doxorubicin-resistant neuroblastoma cells.

Disease Class: Hepatocellular carcinoma [1]

• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vivo Model: Immunodeficient NCr nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Chromatin immunoprecipitation assay
• Experiment for Drug Resistance: Cell titer glo assay assay
• Mechanism Description: Hypermethylation of the miR-137 promoter and negative regulation of miR-137 by CAR contribute in part to reduced miR-137 expression and increased CAR and MDR1 expression in doxorubicin-resistant neuroblastoma cells.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Brain cancer [ICD-11: 2A00]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Nervous tissue
• The Specified Disease: Brain cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.22E-07; Fold-change: -8.03E-02; Z-score: -3.74E-01
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.50E-01; Fold-change: 3.19E-02; Z-score: 2.90E-01
• The Studied Tissue: White matter
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.21E-03; Fold-change: -2.45E-01; Z-score: -1.55E+00
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Neuroectodermal tumor
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.00E-04; Fold-change: -4.73E-01; Z-score: -1.75E+00

Colon cancer [ICD-11: 2B90]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Colon
• The Specified Disease: Colon cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.76E-02; Fold-change: -4.54E-02; Z-score: -2.26E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 8.29E-01; Fold-change: -2.71E-02; Z-score: -1.84E-01

Liver cancer [ICD-11: 2C12]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Liver
• The Specified Disease: Liver cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.11E-12; Fold-change: -1.08E+00; Z-score: -1.65E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.20E-22; Fold-change: -5.67E-01; Z-score: -1.21E+00
• The Expression Level of Disease Section Compare with the Other Disease Section: p-value: 4.82E-02; Fold-change: -1.40E+00; Z-score: -1.64E+00

References

• Ref 1: miR-137 regulates the constitutive androstane receptor and modulates doxorubicin sensitivity in parental and doxorubicin-resistant neuroblastoma cells. Oncogene. 2014 Jul 10;33(28):3717-29. doi: 10.1038/onc.2013.330. Epub 2013 Aug 12.