PPARγ/CCL20 signaling axis promotes cell migration and invasion in hepatocellular carcinoma
Objective To investigate the effect of C-C motif chemokine ligand 20(CCL20)on the migration and invasion of liver cancer cells and its molecular mechanism,so as to provide a basis for the development of new therapeutic targets for liver cancer.Methods Gene Expression Omnibus(GEO)database and immunohistochemical staining were used to explore the expression level of CCL20 in liver cancer tissues and its effect on the survival of patients.A plasmid was used to overexpress CCL20,and the overexpression effi-ciency was identified by real-time PCR and immunoblotting.The effect of CCL20 on the migration and invasion of liver cancer cells was detected by Transwell assay.TIMER2.0 database was used to analyze the correlation between CCL20 expression level and immune cell infiltration in liver cancer tissues.The Cancer Genome Atlas Liver Hepatocellular Carcinoma(TCGA-LIHC)dataset and Cistrome da-tabase were used to identify the upstream regulator of CCL20,its expression levels in liver cancer tissues,and its effects on patient sur-vival.The effects of upstream regulatory factors on CCL20 expression and cell function were detected by Transwell and real-time PCR.Results CCL20 gene was highly expressed in liver cancer tissues(P＜0.001),and the high expression of CCL20 was associated with a shorter survival time(P＜0.05).The protein level of CCL20 in liver cancer tissues was also significantly increased(P＜0.001).Over-expression of CCL20 could promote the migration and invasion of hepatocellular carcinoma(P＜0.001).CCL20 is associated with im-mune invasion of liver cancer cells(P＜0.05).CCL20 was positively correlated with immune infiltration of regulatory T cells in liver cancer(P＜0.05).Peroxisome proliferative activated receptor gamma(PPARγ)was the upstream transcription factor of CCL20.PPARγ was highly expressed in liver cancer tissues and was associated with shorter survival in patients(P＜0.05).Interference with PPARγ could inhibit CCL20 expression,migration and invasion of liver cancer cells(P＜0.05).Conclusion The PPARγ/CCL20 sig-naling axis can promote cell migration and invasion in liver cancer,which may be a potential therapeutic target.
万方数据
维普
