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.

越来越多的证据表明，与癌症相关的成纤维细胞（CAF）在子宫内膜癌（EC）发病机理中起着至关重要的作用。本研究调查了从CAFs在EC中释放的细胞外囊泡（EV）封装的miR-320a的临床意义和生物学功能。从GSE25405数据库获得与EC相关的微阵列数据，并进行差异分析。检测到miR-320a在CAF和正常子宫内膜成纤维细胞（NFs）以及CAF输送的EV中的表达；同样，观察到miR-320a从CAF向EC细胞的递送。此外，我们通过双荧光素酶报告基因检测证实miR-320a靶向HIF1α。表型分析用于研究EV传递的miR-320a的功能意义及其下游效应。发现miR-320a在EC细胞和组织中低表达。成功分离出CAF分泌的电动汽车，并且发现在这些电动汽车中miR-320a也以低水平表达。最后，我们发现CAF分泌的外泌体miR-320a直接转移至EC细胞，从而抑制了它们的增殖。从机制上讲，我们发现这是由于miR-320a下调了HIF1α，导致VEGFA表达降低体外。因此，我们过表达的HIF1α还表明miR-320a过表达在EC细胞中的抑制作用可以逆转。这些结果表明，携带过量表达的miR-320a的CAF衍生电动汽车是EC治疗策略的新方向。