RETRACTED: miR-135b Delivered by Gastric Tumor Exosomes Inhibits FOXO1 Expression in Endothelial Cells and Promotes Angiogenesis (Retracted article. See vol. 30, pg. 2636, 2022)

Exosomes, which act as mediators of intercellular communication, are nanoscale membrane vesicles that contain proteins, lipids, mRNAs, and microRNAs (miRNAs). Additionally, exosomes play a significant role in the development of tumors. The robust angiogenesis of gastric cancer (GC) is one of the reasons for its rampant growth. Drugs and other treatments are not good solutions for the problem of angiogenesis in GC. Here we found that exosome-delivered miRNA contributes greatly to angiogenesis in GC. The downregulation of forkhead box O1 (FOXO1) was observed in GC. After measurement of lentivirus overexpressing microRNA-135b (miR-135b) levels, we found that miR-135b and FOXO1 are negatively correlated. In addition, miR-135b was delivered to tumor cells by exosomes to take its effect on angiogenesis in GC. Exosome-containing cell cocultures and a tumor-implanted mouse model were used for in vitro and in vivo studies, respectively. We showed that miR-135b derived from GC cells suppressed the expression of FOXO1 protein and enhanced the growth of blood vessels. Our findings illustrate a novel signaling pathway comprising exosomes, miRNAs, and target genes, and they provide potential targets for anti-angiogenic therapy.