Molecule Information

General Information of the Molecule (ID: Mol00103)

• Name: Transcription factor Jun (JUN) ,Homo sapiens
• Synonyms: Activator protein 1; AP1; Proto-oncogene c-Jun; Transcription factor AP-1 subunit Jun; V-jun avian sarcoma virus 17 oncogene homolog; p39
• Molecule Type: Protein
• Gene Name: JUN
• Gene ID: 3725
• Location: chr1:58776845-58784048[-]
• Sequence:
  MTAKMETTFYDDALNASFLPSESGPYGYSNPKILKQSMTLNLADPVGSLKPHLRAKNSDL
  LTSPDVGLLKLASPELERLIIQSSNGHITTTPTPTQFLCPKNVTDEQEGFAEGFVRALAE
  LHSQNTLPSVTSAAQPVNGAGMVAPAVASVAGGSGSGGFSASLHSEPPVYANLSNFNPGA
  LSSGGGAPSYGAAGLAFPAQPQQQQQPPHHLPQQMPVQHPRLQALKEEPQTVPEMPGETP
  PLSPIDMESQERIKAERKRMRNRIAASKCRKRKLERIARLEEKVKTLKAQNSELASTANM
  LREQVAQLKQKVMNHVNSGCQLMLTQQLQTF
• Function: Transcription factor that recognizes and binds to the AP-1 consensus motif 5'-TGA[GC]TCA-3'. Heterodimerizes with proteins of the FOS family to form an AP-1 transcription complex, thereby enhancing its DNA binding activity to the AP-1 consensus sequence 5'-TGA[GC]TCA-3' and enhancing its transcriptional activity. Together with FOSB, plays a role in activation-induced cell death of T cells by binding to the AP-1 promoter site of FASLG/CD95L, and inducing its transcription in response to activation of the TCR/CD3 signaling pathway. Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. Involved in activated KRAS-mediated transcriptional activation of USP28 in colorectal cancer (CRC) cells. Binds to the USP28 promoter in colorectal cancer (CRC) cells.
• Uniprot ID: JUN_HUMAN
• Ensembl ID: ENSG00000177606
• HGNC ID: HGNC:6204

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

Cisplatin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Non-small cell lung cancer [1]

• Sensitive Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: c-Jun/BCL-xl signaling pathway; Inhibition; hsa04210
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; Luciferase reporter assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Overexpression of miR216b sensitizes NSCLC cells to cisplatin-induced apoptosis by decreasing the expression of c-Jun and inhibiting the c-Jun/Bcl-xl pathway.

Disease Class: Ovarian cancer [2]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Sensitive Drug: Cisplatin
• 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 viability; Inhibition; hsa05200
• Cell Pathway Regulation: c-Jun/BCL-xl signaling pathway; Regulation; hsa04210
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vivo Model: BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Recovery of miR-139-5p suppressed the expression of c-Jun and thus reversed cisplatin-resistance in ovarian cancer.

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: Expression; 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

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: 4.99E-18; Fold-change: -5.46E-01; Z-score: -7.32E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 3.17E-12; Fold-change: -5.36E-01; Z-score: -6.36E-01

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: 1.79E-02; Fold-change: -8.04E-01; Z-score: -8.40E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 9.03E-01; Fold-change: -4.26E-02; Z-score: -4.00E-02

References

• Ref 1: Overexpression of miR-216b sensitizes NSCLC cells to cisplatin-induced apoptosis by targeting c-Jun. Oncotarget. 2017 Oct 27;8(61):104206-104215. doi: 10.18632/oncotarget.22171. eCollection 2017 Nov 28.
• Ref 2: Recovery of miR-139-5p in Ovarian Cancer Reverses Cisplatin Resistance by Targeting C-Jun. Cell Physiol Biochem. 2018;51(1):129-141. doi: 10.1159/000495169. Epub 2018 Nov 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.