Molecule Information

General Information of the Molecule (ID: Mol00099)

• Name: Interleukin-6 (IL6) ,Homo sapiens
• Synonyms: IL-6; B-cell stimulatory factor 2; BSF-2; CTL differentiation factor; CDF; Hybridoma growth factor; Interferon beta-2; IFN-beta-2; IFNB2
• Molecule Type: Protein
• Gene Name: IL6
• Gene ID: 3569
• Location: chr7:22725884-22732002[+]
• Sequence:
  MNSFSTSAFGPVAFSLGLLLVLPAAFPAPVPPGEDSKDVAAPHRQPLTSSERIDKQIRYI
  LDGISALRKETCNKSNMCESSKEALAENNLNLPKMAEKDGCFQSGFNEETCLVKIITGLL
  EFEVYLEYLQNRFESSEEQARAVQMSTKVLIQFLQKKAKNLDAITTPDPTTNASLLTKLQ
  AQNQWLQDMTTHLILRSFKEFLQSSLRALRQM
• Function: Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the intracellular IL6-signaling pathway (Probable). The interaction with the membrane-bound IL6R and IL6ST stimulates 'classic signaling', whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells (Probable).
• Uniprot ID: IL6_HUMAN
• Ensembl ID: ENSG00000136244
• HGNC ID: HGNC:6018

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

Type(s) of Resistant Mechanism of This Molecule

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

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

Cisplatin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Esophageal squamous cell carcinoma [1]

• Sensitive Disease: Esophageal squamous cell carcinoma [ICD-11: 2B70.3]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: IL6/STAT3 signaling signaling pathway; Inhibition; hsa04659
• In Vitro Model: TE8 cells; Esophageal; Homo sapiens (Human); CVCL_1766
• In Vitro Model: TE13 cells; Esophageal; Homo sapiens (Human); CVCL_4463
• In Vitro Model: TE10 cells; Esophagus; Homo sapiens (Human); CVCL_1760
• In Vitro Model: TE1 cells; Esophagus; Homo sapiens (Human); CVCL_1759
• In Vitro Model: TE11 cells; Esophagus; Homo sapiens (Human); CVCL_1761
• In Vitro Model: TE5 cells; Esophagus; Homo sapiens (Human); CVCL_1764
• In Vitro Model: TE9 cells; Esophagus; Homo sapiens (Human); CVCL_1767
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Let-7c directly repressed cisplatin-activated interleukin (IL) -6/STAT3 prosurvival pathway, restored sensitivity to cisplatin and increased rate of apoptosis after exposure to cisplatin.

Sorafenib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Renal cell carcinoma [2]

• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sorafenib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell cytotoxicity; Activation; hsa04650
• Cell Pathway Regulation: Tumorigenesis; Inhibition; hsa05200
• In Vitro Model: 786-O cells; Kidney; Homo sapiens (Human); CVCL_1051
• In Vitro Model: A498 cells; Kidney; Homo sapiens (Human); CVCL_1056
• In Vitro Model: Caki-2 cells; Kidney; Homo sapiens (Human); CVCL_0235
• In Vitro Model: OSRC-2 cells; Kidney; Homo sapiens (Human); CVCL_1626
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Long noncoding RNA-SRLR elicits intrinsic sorafenib resistance via evoking IL-6/STAT3 axis in renal cell carcinoma. LncRNA-SRLR directly binds to NF-kB and promotes IL-6 transcription, leading to the activation of STAT3 and the development of sorafenib tolerance.

Investigative Drug(s) 1 drug(s) in total

Platinum

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [3]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Platinum
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Caspase 3/7 cleavage assays; Aldefluor assay; MTS assay; Flow cytometric analysis
• Mechanism Description: Blocking the EZH2-interactiing domain of HOTAIR and disrupting the HOTAIR-EZH2 interaction resensitizes cancer cells to clinically relevant cytotoxic chemotherapies, reduces cell invasion and decreases NF-kB transcriptional activity and IL-6 and MMP-9 expression in vivo. Levels of genes like IL6 shown to be up-regulated by HOTAIR.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Esophageal cancer [ICD-11: 2B70]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Esophagus
• The Specified Disease: Esophageal cancer
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 9.38E-02; Fold-change: -3.84E+00; Z-score: -1.59E+00

Breast cancer [ICD-11: 2C60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Breast tissue
• The Specified Disease: Breast cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.49E-12; Fold-change: -2.64E-01; Z-score: -1.83E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 4.31E-08; Fold-change: -1.61E+00; Z-score: -1.03E+00

Kidney cancer [ICD-11: 2C90]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Kidney
• The Specified Disease: Kidney cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.23E-04; Fold-change: 4.48E-01; Z-score: 7.59E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 2.88E-05; Fold-change: 1.74E-01; Z-score: 2.54E-01

References

• Ref 1: Let-7 expression is a significant determinant of response to chemotherapy through the regulation of IL-6/STAT3 pathway in esophageal squamous cell carcinoma. Clin Cancer Res. 2012 Sep 15;18(18):5144-53. doi: 10.1158/1078-0432.CCR-12-0701. Epub 2012 Jul 30.
• Ref 2: Long noncoding RNA-SRLR elicits intrinsic sorafenib resistance via evoking IL-6/STAT3 axis in renal cell carcinoma. Oncogene. 2017 Apr 6;36(14):1965-1977. doi: 10.1038/onc.2016.356. Epub 2016 Nov 14.
• Ref 3: Therapeutic targeting using tumor specific peptides inhibits long non-coding RNA HOTAIR activity in ovarian and breast cancer. Sci Rep. 2017 Apr 18;7(1):894. doi: 10.1038/s41598-017-00966-3.