Circulating RNAs, circ_4911 and circ_4302, are novel regulators of endothelial cell function under a hepatocellular carcinoma microenvironment

Abstract

Hepatocellular carcinoma (HCC) is a common hypervascular tumor disease. Endothelial cells, as a crucial component of the tumor microenvironment, have been reported to participate in angiogenesis and influence the development of tumors, including HCC. Recent studies have demonstrated that circulating RNAs (circRNAs) participate in the functional regulation of endothelial cells. However, the expression and function of circRNAs in endothelial cells under the HCC microenvironment is still unclear. In the present study, we analyzed the expression profiles and investigated the role of circRNAs in human umbilical vein endothelial cells (HUVECs) co-cultured with human primary hepatoma cells. Based on an RNA-sequencing assay, we screened 19 significantly downregulated circRNAs in HUVECs under an HCC microenvironment. Subsequently, we validated the expression of the candidate circRNAs using RT-qPCR, and selected two of the most downregulated circRNAs among them, circ_4911 and circ_4302. Next, through circRNA overexpression experiments, we demonstrated that overexpression of circ_4911 and circ_4302 both inhibited the proliferation and migration of HUVECs, and arrested cells at the GO/G1 stage, while promoting adhesion. Overall, in the present study, we identified the roles of circ_4911 and circ_4302 in regulating functions of HUVECs under an HCC microenvironment.