IL-17a promotes hepatocellular carcinoma by increasing FAP expression in hepatic stellate cells via activation of the STAT3 signaling pathway

Abstract

Abstract Studies have shown that hepatic stellate cells (HSCs) and interleukin-17a (IL-17a) play important roles in liver tumorigenesis. In addition, fibroblast activation protein-α (FAP) has been shown to be a key regulator of hepatic stellate cell activation. In this study, in vivo and in vitro experiments were performed to verify the promoting effects of IL-17a administration, IL-17a overexpression, and FAP upregulation in HSCs on liver fibrosis and liver tumorigenesis. The cleavage under targets & release using nuclease (CUT&RUN) technique was used to verify the binding status of STAT3 to the FAP promoter. The in vitro studies showed that IL-17a activated HSCs and promoted HCC development and progression. FAP and IL-17a overexpression also activated HSCs, promoted HCC cell proliferation and migration, and inhibited HCC cell apoptosis. The in vivo studies suggested that IL-17a and FAP overexpression in HSCs facilitated liver tumor development and progression. The CUT&RUN results indicated that FAP expression was regulated by STAT3, which could bind to the FAP promoter region and regulate its transcription status. We concluded that IL-17a promoted HCC by increasing FAP expression in HSCs via activation of the STAT3 signaling pathway.