ATAD2 silencing decreases VEGFA secretion through targeting has-miR-520a to inhibit angiogenesis in colorectal cancer

Abstract

ATPase family AAA domain-containing protein 2 (ATAD2) is involved in various types of cancers, including colorectal cancer. This study aimed to determine the role of ATAD2 in angiogenesis in colorectal cancer. Here, we downregulated ATAD2 expression in HCT116 and SW480 cells, and collected the conditioned medium (CM) from control and ATAD2-silenced cells. The effect of CM on human umbilical vein endothelial cells (HUVEC) was evaluated by using CCK-8, wound healing, tube formation, Western blot, and dual-luciferase reporter assays. Our results showed that the proliferation, migration, and tube formation of HUVEC were reduced in presence of ATAD2-silenced CM, and the levels of phosphorylated vascular endothelial growth factor receptor 2 (P-VEGFR2), CD31, and CD34 were downregulated. Mechanism studies showed that ATAD2 silencing regulated the expression of vascular endothelial growth factor A (VEGFA) and miR-520a. Moreover, we found that miR-520a could bind to ATAD2, and its inhibitor partly reversed the alterations in HUVEC induced by CM from ATAD2-silenced cells. In addition, we demonstrated that miR-520a directly bound to 3′-UTR of VEGFA and inhibited its expression. Collectively, our results indicate that ATAD2 inhibition suppresses VEGFA secretion by increasing miR-520a levels. Our study suggests ATAD2 as a potential therapeutic target for angiogenesis in colorectal cancer.