Transcriptomic analyses of chemokines reveal that down-regulation of XCR1 is associated with advanced hepatocellular carcinoma

Abstract

Chemokines are essential coordinators of cellular migration and cell-cell interactions, therefore considerable attention has been paid to the application of chemokines to cancer immunotherapy. In this study, we screened for the expression levels of 58 human chemokines/chemokine receptors in hepatocellular carcinoma (HCC) by using samples from the TCGA LIHC cohort and found 16 consistently down-regulated and 11 up-regulated chemokine genes in HCC compared with normal samples. Furthermore, the expressions of XCR1 were verified by Western blot in liver cancer cell lines. We used CCK8, plate cloning formation, scratch-wound and transwell analysis to measure the ability of proliferation, metastasis and invasion, respectively. Protein expression was analyzed by cell immunofluorescence and western-blot. We found that silencing XCR1 promoted, while overexpressing XCR1 inhibited, HCC cell migration and invasion in vitro, its mechanism may involve in inhibition of Epithelial Mesenchymal Transition (EMT). However, the overexpression of XCR1 in HCCLM3 in vitro can restrain the growth partially due to the inhibition of MAPK and PI3K/AKT signaling pathway. Gene Set Enrichment Analysis (GSEA) showed that high expression of XCR1 is positively associated with EMT, which is closely associated with tumor migration and invasion. Our study provides the basis for further investigation of the molecular mechanism by which down-regulation of XCR1 promotes the development and progression of HCC.