CXCL13 Regulates The Expression Of PD-L1 In Colorectal Cancer Cells Through AKT Axis

Objective: To investigate the effect of chemokine CXCL13 on the proliferation,migration and invasion of colorectal cancer cells and its possible mechanism,and to explore the possible relationship between CXCL13 and immune checkpoint PD-L1 and its mechanism.Methods: CXCL13 expression differential gene analysis and KEGG pathway enrichment analysis were completed by using TCGA database complete transcriptome data of colorectal cancer.CXCR5 expression in colorectal cancer cells and normal intestinal mucosa cell lines was detected by Western Blot assay.The effects of different concentrations of CXCL13 on the proliferation of colorectal cancer cells were detected by CCK-8 and cell cloning experiments.The effect of CXCL13 on the migration ability of colorectal cancer cells was detected by cell scratch test.The effect of CXCL13 on the invasion ability of colorectal cancer cells was detected by Transwell invasion assay.Western Blot was used to detect the changes of AKT signal and PD-L1 in colorectal cancer cells under the action of CXCL13.The key role of AKT signal in the regulation of CXCL13 on proliferation,migration and invasion of colorectal cancer cells and PD-L1 expression was determined by MK2206 signal blocking experiment.Results: The expression of CXCL13 in colorectal cancer tissues was significantly positively correlated with PD-L1(R=0.67,p<2.2e-16).KEGG pathway enrichment results suggest that chemokine-activated receptor pathway and PI3K/AKT pathway are the key mechanisms for CXCL13 to play a biological role in colorectal cancer.The expression of CXCR5 in different colorectal cancer cell lines was higher than that in normal intestinal mucosal cells.CXCL13 at a concentration of 70ng/m L can significantly promote the proliferation,invasion and metastasis of colorectal cancer cells.And the activation of AKT signaling protein is the key mechanism.CXCL13 up-regulated the expression of PD-L1 in colorectal cancer cells by activating AKT signaling.Conclusion: 1.CXCL13 promotes the proliferation,migration and invasion of colorectal cancer cells.2.CXCL13 affects the proliferation,migration and invasion of colorectal cancer cells by activating the AKT pathway.3.CXCL13 up-regulated the expression of PD-L1 in colorectal cancer cells through AKT pathway.