IL‐6 upregulates the expression of IL‐6R through the JAK2/STAT3 signalling pathway to promote progression of hepatocellular carcinoma

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.