Exosomes Carrying MicroRNA-155 Target Forkhead Box O3 of Endothelial Cells and Promote Angiogenesis in Gastric Cancer

Abstract

Gastric cancer (GC) has a poor prognosis due to its relentless proliferation and metastasis. One of the reasons for this plight is the formidable angiogenesis ability of GC. Considering the important role of cancer exosomes as carriers and communicators in the tumor microenvironment, we explored the role of exosome-microRNA (miRNA) in regulating angiogenesis. Western blotting and quantitative real-time PCR were used to measure the protein and mRNA levels of the miRNA target gene. To detect changes in cellular biological functions, we pretreated human umbilical vein endothelial cells (HUVECs) that were severally cocultured with GC-derived exosomes and transfected them with different miRNAs directly. Also, we used the mouse xenograft model to verify the effect of miR-155 on angiogenesis of GC tissues in vivo. Our study confirmed that miR-155, as a driver of angiogenesis, encapsulated by exosomes from GC can enhance the generation of new vessels for GC in vitro through inhibiting the expression of Forkhead box O3 (FOXO3a) protein, which led to the progression of GC. Therefore, miR-155 is probable to become a potential biomarker for the detection of migration and angiogenesis of GC, and serves as a novel target for anti-angiogenesis therapy.