Molecule Information

General Information of the Molecule (ID: Mol00130)

• Name: Nuclear receptor subfamily 2 group C2 (NR2C2) ,Homo sapiens
• Synonyms: Orphan nuclear receptor TAK1; Orphan nuclear receptor TR4; Testicular receptor 4; TAK1; TR4
• Molecule Type: Protein
• Gene Name: NR2C2
• Gene ID: 7182
• Location: chr3:14947583-15053600[+]
• Sequence:
  MTSPSPRIQIISTDSAVASPQRIQIVTDQQTGQKIQIVTAVDASGSPKQQFILTSPDGAG
  TGKVILASPETSSAKQLIFTTSDNLVPGRIQIVTDSASVERLLGKTDVQRPQVVEYCVVC
  GDKASGRHYGAVSCEGCKGFFKRSVRKNLTYSCRSNQDCIINKHHRNRCQFCRLKKCLEM
  GMKMESVQSERKPFDVQREKPSNCAASTEKIYIRKDLRSPLIATPTFVADKDGARQTGLL
  DPGMLVNIQQPLIREDGTVLLATDSKAETSQGALGTLANVVTSLANLSESLNNGDTSEIQ
  PEDQSASEITRAFDTLAKALNTTDSSSSPSLADGIDTSGGGSIHVISRDQSTPIIEVEGP
  LLSDTHVTFKLTMPSPMPEYLNVHYICESASRLLFLSMHWARSIPAFQALGQDCNTSLVR
  ACWNELFTLGLAQCAQVMSLSTILAAIVNHLQNSIQEDKLSGDRIKQVMEHIWKLQEFCN
  SMAKLDIDGYEYAYLKAIVLFSPDHPGLTSTSQIEKFQEKAQMELQDYVQKTYSEDTYRL
  ARILVRLPALRLMSSNITEELFFTGLIGNVSIDSIIPYILKMETAEYNGQITGASL
• Function: Orphan nuclear receptor that can act as a repressor or activator of transcription. An important repressor of nuclear receptor signaling pathways such as retinoic acid receptor, retinoid X, vitamin D3 receptor, thyroid hormone receptor and estrogen receptor pathways. May regulate gene expression during the late phase of spermatogenesis. Together with NR2C1, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription including that of GATA1. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Plays a fundamental role in early embryonic development and embryonic stem cells. Required for normal spermatogenesis and cerebellum development. Appears to be important for neurodevelopmentally regulated behavior (By similarity). Activates transcriptional activity of LHCG. Antagonist of PPARA-mediated transactivation.
• Uniprot ID: NR2C2_HUMAN
• Ensembl ID: ENSG00000177463
• HGNC ID: HGNC:7972

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

Doxorubicin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Hepatocellular carcinoma [1]

• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: NF-kappaB signaling pathway; Inhibition; hsa04064
• In Vitro Model: QGY-7703 cells; Liver; Homo sapiens (Human); CVCL_6715
• In Vitro Model: MHCC97-H cells; Liver; Homo sapiens (Human); CVCL_4972
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-26b suppresses NF-kB signaling and thereby sensitized HCC cells to the doxorubicin-induced apoptosis by inhibiting the expression of TAk1 and TAB3.

Fluorouracil

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Hepatocellular carcinoma [2]

• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Resistant Drug: Fluorouracil
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: Huh-7 cells; Liver; Homo sapiens (Human); CVCL_0336
• In Vitro Model: BEL-7402 cells; Liver; Homo sapiens (Human); CVCL_5492
• In Vitro Model: SMMC7721 cells; Uterus; Homo sapiens (Human); CVCL_0534
• In Vitro Model: Skhep1 cells; Liver; Homo sapiens (Human); CVCL_0525
• In Vitro Model: MHCC97-H cells; Liver; Homo sapiens (Human); CVCL_4972
• In Vitro Model: HCC-LM3 cells; Liver; Homo sapiens (Human); CVCL_6832
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8; Flow cytometry assay; EdU assay
• Mechanism Description: Ectopic expression of SNHG6-003 in HCC cells promoted cell proliferation and induced drug resistance, whereas SNHG6-003 knockdown promoted apoptosis. Moreover, SNHG6-003 functioned as a competitive endogenous RNA (ceRNA), effectively becoming sponge for miR-26a/b and thereby modulating the expression of transforming growth factor-beta-activated kinase 1 (TAk1). Importantly, expression analysis revealed that both SNHG6-003 and TAk1 were upregulated in human cancers, exhibiting a co-expression pattern. In HCC patients, high expression of SNHG6-003 closely correlated with tumor progression and shorter survival.

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

Calycosin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Nasopharyngeal carcinoma [3]

• Sensitive Disease: Nasopharyngeal carcinoma [ICD-11: 2B6B.0]
• Sensitive Drug: Calycosin
• Molecule Alteration: Phosphorylation; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: TRAF6-related signaling pathway; Regulation; hsa05206
• In Vitro Model: CNE2 cells; Nasopharynx; Homo sapiens (Human); CVCL_6889
• In Vitro Model: C666-1 cells; Throat; Homo sapiens (Human); CVCL_7949
• In Vitro Model: CNE1 cells; Throat; Homo sapiens (Human); CVCL_6888
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; BrdU assay
• Mechanism Description: Calycosin inhibits nasopharyngeal carcinoma cells by downregulating EWSAT1 expression to regulate the TRAF6-related pathways.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

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: 2.03E-05; Fold-change: 2.99E-01; Z-score: 7.65E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 3.21E-05; Fold-change: 1.48E-01; Z-score: 3.12E-01
• The Expression Level of Disease Section Compare with the Other Disease Section: p-value: 3.00E-01; Fold-change: 1.84E-01; Z-score: 4.31E-01

References

• Ref 1: MicroRNA-26b suppresses the NF-kB signaling and enhances the chemosensitivity of hepatocellular carcinoma cells by targeting TAK1 and TAB3. Mol Cancer. 2014 Feb 24;13:35. doi: 10.1186/1476-4598-13-35.
• Ref 2: The long non-coding RNA, SNHG6-003, functions as a competing endogenous RNA to promote the progression of hepatocellular carcinoma. Oncogene. 2017 Feb 23;36(8):1112-1122. doi: 10.1038/onc.2016.278. Epub 2016 Aug 15.
• Ref 3: Calycosin inhibits nasopharyngeal carcinoma cells by influencing EWSAT1 expression to regulate the TRAF6-related pathways. Biomed Pharmacother. 2018 Oct;106:342-348. doi: 10.1016/j.biopha.2018.06.143. Epub 2018 Jul 11.