Upregulation of exosomal microRNA-21 in pancreatic stellate cells promotes pancreatic cancer cell migration and enhances Ras/ERK pathway activity

Pancreatic stellate cells (PSCs) are typically activated in pancreatic ductal adenocarcinoma (PDAC) and release exosomes containing high levels of microRNA-21 (miR-21). However, the specific roles of exosomal miR-21 in regulating the PDAC malignant phenotype remain unknown. The present study aimed to determine the effects of exosomal miR-21 on the migratory ability of PDAC cells and explore the potential underlying molecular mechanism. Weighted gene correlation network and The Cancer Genome Atlas database analysis revealed that high miR-21 levels were associated with a poor prognosis in patients with pancreatic adenocarcinoma, and that the Ras/ERK signaling pathway may be a potential target of miR-21. In vitro, PDAC cells were demonstrated to internalize the PSC-derived exosome, resulting in high miR-21 levels, which subsequently promoted cell migration, induced epithelial-to-mesenchymal transition (EMT) and increased matrix metalloproteinase-2/9 activity. In addition, exosomal miR-21 increased the levels of ERK1/2 and Akt phosphorylation in PDAC cells. Collectively, these results suggested that PSC-derived exosomal miR-21 may promote PDAC cell migration and EMT and enhance Ras/ERK signaling activity. Thus, miR-21 may be a potential cause of poor prognosis in patients with pancreatic cancer and a new treatment target.