Upregulation of exosomal microRNA‑21 in pancreatic stellate cells promotes pancreatic cancer cell migration and enhances Ras/ERK pathway activity
Qiang Ma, Huanwen Wu, Ying Xiao, Zhiyong Liang, Tonghua Liu
Abstract
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.