RGC-32 induces the imbalance of Treg/Th17 by regulating Wnt/β-catenin signaling in patients with liver cancer
Objective:To investigate the correlation between the level of RGC-32 and the ratio of Treg/Th17 cells in patients with liver cancer,and to explore the regulatory effect of RGC-32 on Wnt/β-catenin signaling pathway.Methods:The expression levels of RGC-32,IL-17,IL-22,TGF-β1 and IL-10 in plasma of healthy controls and liver cancer patients were detected by ELISA.Flow cytometry was used to detect Th17 cells and Treg cells in peripheral blood of healthy controls and patients with liver cancer.The level of RGC-32 in mononuclear cells(PMBC)was reduced by siRNA transfection,and the effect of RGC-32 knockdown on Wnt/β-catenin signaling pathway was detected by Western blot.Results:Compared with healthy controls,the level of RGC-32 in liver cancer patients was significantly increased(P<0.01),the number of Th17 cells was increased while the number of Treg cells was decreased,and the ratio of Treg/Th17 cells was significantly decreased(P<0.01).Compared with healthy controls,the proinflammatory cytokines IL-17 and IL-22 secreted by Th17 cells were significantly increased in liver cancer patients(P<0.01),while the anti-inflammatory cytokines TGF-β1 and IL-10 secreted by Treg cells were significantly decreased(P<0.01).By linear regression analysis,the results showed that there was no correlation between the level of RGC-32 and Treg/Th17 in healthy controls(P>0.05),but a negative correlation between the level of RGC-32 and Treg/Th17 in patients with liver cancer(P<0.01).After knockdown of RGC-32,the expression of pro-inflammatory cytokine IL-17 was decreased(P<0.01),the expression of anti-inflammatory cytokine TGF-β1 was increased(P<0.01),and the activation of Wnt/β-catenin signal was inhibited.Conclusion:The up-regulation of RGC-32 leads to the imbalance of Treg/Th17 cells in patients with liver cancer,and the down-regulation of RGC-32 can inhibit the activation of Wnt/β-catenin signal.
response gene to complement 32cellular immunityregulatory T cellsliver cancer