IL-6 upregulates the expression of IL-6R through the JAK2/STAT3 signalling pathway to promote progression of hepatocellular carcinoma.
Scand J Immunol
; 98(1): e13271, 2023 Jul.
Article
en En
| MEDLINE
| ID: mdl-38441314
ABSTRACT
The progression of hepatocellular carcinoma (HCC) involves multifactor, multistep interactions. High expression of interleukin-6 receptor (IL-6R) plays an important role in the occurrence and development of tumours, but the regulatory mechanism of IL-6R expression and its function in HCC have not been fully defined. Western blot was used to evaluate the phosphorylation of key kinases in the JAK2/STAT3 pathway and the protein expression levels of related proliferation molecules, migration molecules and apoptotic molecules. The antiapoptosis, migration and proliferation of cells of each group were analysed with JC-1 to judge the cell apoptosis rate, the EdU method to determine the proliferation vitality of the cells, clone formation experiments and Transwell experiments. High expression of IL-6R in cell lines, lower protein levels of the apoptotic molecules c-Caspase7 and c-Caspase3 and higher protein levels of the proliferative molecules p-P70S6K and migration molecules MMP9 and MMP2 were consistent with stronger antiapoptosis, proliferation and migration. Interestingly, IL-6 upregulated the expression of IL-6R by activating the JAK2/STAT3 signalling pathway. Also, the expression of IL-6R protein was downregulated after lentivirus knockdown of STAT3. In nude mice bearing subcutaneous tumours, upregulation of IL-6R expression after activation of the JAK2/STAT3 signalling pathway by IL-6 significantly increased tumour growth. Moreover, the expression of IL-6R protein was downregulated, and the terminal tumour volume was significantly downregulated in the lentiviral STAT3 knockdown group. IL-6 regulated the transcription of IL-6R through the activation of the JAK2/STAT3 signalling pathway.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Carcinoma Hepatocelular
/
Neoplasias Hepáticas
Límite:
Animals
Idioma:
En
Revista:
Scand J Immunol
Año:
2023
Tipo del documento:
Article
País de afiliación:
China