miR-655-3p Regulates the Vascular Endothelial Growth Factor A/AKT Serine Signaling Pathway via ATAD2 to Inhibit the Proliferation, Invasion, and Angiogenesis of Pancreatic Ductal Carcinoma Cells

Abstract

miR-655-3p has been reported to play crucial roles in the development and progression of tumorigenesis and development. In this study, we investigated the potential biological role of miR-655-3p in pancreatic ductal carcinoma (PDAC). After PDAC cells were transfected with miR-655-3p, cell proliferation, migration and invasion were evaluated. The targeting relationship between miR-655-3p and ATAD2 was verified. A xenograft tumor model was established to evaluate the role of miR-655-3p in tumorigenesis abilities in vivo. Immunohistochemical staining was used to detect the levels of Ki-67, CD31, ATAD2, and VEGFA. We found that miR-655-3p inhibited PDAC cell proliferation, migration, and invasion and decreased the ability of HUVECs to form tubes by decreasing the VEGFA/AKT signaling pathway. Moreover, we predicted and verified that ATAD2, the direct target gene of miR-655-3p, could reverse the inhibitory effect caused by miR-655-3p overexpression. Additionally, we demonstrated that miR-655-3p suppressed PDAC growth and angiogenesis in vivo, characterized by decreased tumor volume, mass, and levels of Ki-67, CD31, ATAD2, and VEGFA. These results show that miR-655-3p might serve as a tumor suppressor in PDAC by targeting ATAD mediated-VEGFA/AKT signaling pathway, which may provide a potential therapeutic candidate for PDAC.