M2 macrophage facilitated angiogenesis in cutaneous squamous cell carcinoma via circ_TNFRSF21/miR‐3619‐5p/ROCK axis

Abstract

Abstract In recent years, the role of circular RNA in cancer cells has been studied broadly; however, the functional significance of circular RNA in the regulation of the tumor microenvironment (TME) is not fully understood. In this study, we aimed to reveal the role of circ_TNFRSF21 in M2 macrophage‐induced cutaneous squamous cell carcinoma (cSCC) angiogenesis. Quantitative polymerase chain reaction and Western blotting were performed to determine the levels of the indicated genes. Direct binding between circ_TNFRSF21 and miR‐3619‐5p, miR‐3619‐5p, and ROCK2 was verified by dual‐luciferase activity. The migration and invasion of human umbilical vein endothelial cells were evaluated by wound healing and transwell assays. Tube formation was performed to detect in vitro angiogenesis. Circ_TNFRSF21 and ROCK2 were upregulated in cSCC tissue, while miR‐3619‐5p was downregulated. Circ_TNFRSF21 negatively regulated the expression of miR‐3619‐5p, while miR‐3619‐5p negatively regulated the expression of ROCK2. miR‐3619‐5p suppressed tube formation by inhibiting ROCK signaling. M2 macrophages facilitated tube formation via the circ_TNFRSF21/miR‐3619‐5p/ROCK2 axis. Our present study revealed that circ_TNFRSF21 was elevated in M2 macrophages and mediated M2 macrophage‐induced tube formation in vitro.

Keywords

• angiogenesis
• circ_TNFRSF21
• miR‐3619‐5p
• ROCK2
• tumor‐associated macrophages