Extracellular vesicle encapsulated microRNA-320a inhibits endometrial cancer by suppression of the HIF1α/VEGFA axis.

Abstract Accumulating evidence indicates that cancer-associated fibroblasts (CAFs) play a crucial role in endometrial cancer (EC) pathogenesis. The present study investigated the clinical significance and biological function of extracellular vesicle (EV) encapsulated miR-320a released from CAFs in EC. EC-related microarray data was obtained from the GSE25405 database and differential analysis was performed. Expression of miR-320a in CAFs and normal endometrial fibroblasts (NFs) as well as CAF-delivered EVs was detected; also, delivery of miR-320a from CAFs to EC cells was observed. In addition we confirmed that miR-320a targets HIF1α via a dual-luciferase reporter assay. Phenotypic analysis was used to study the functional significance of EV delivered miR-320a and its downstream effects. miR-320a was found to have low expression in EC cells and tissues. CAF-secreted EVs were successfully isolated and miR-320a was found also be expressed at low levels in these EVs. Finally, we found direct transfer of CAF-secreted exosomal miR-320a to EC cells, which inhibited their proliferation. Mechanistically, we found this is due to downregulation of HIF1α by miR-320a, which led to lowered VEGFA expression in vitro. Accordingly, we overexpressed HIF1α also showed that the inhibitory effect of miR-320a overexpression in EC cells could be reversed. These results point to CAF-derived EVs carrying overexpressed miR-320a as a novel direction for therapeutic strategies for EC.