Aims
To explore the pro-metastatic role of exosomes derived from highly invasive pancreatic cancer cell and the associated aberrant expression of exosomal microRNAs (miRNAs). Main
Methods
Weakly invasive PC-1 cells were treated with exosomes of highly invasive PC-1.0 cells to determine the pro-metastatic effect of PC-1.0 derived exosomes. The exosomal miRNA profile was further investigated using high-throughput sequencing. The level of miR-125b-5p in highly and weakly invasive pancreatic cancer cells was further determined. Pancreatic cancer cells transfected with miR-125b-5p mimic and inhibitor were used to explore the effect of miR-125b-5p on migration, invasion and epithelial-to-mesenchymal transition (EMT). Treatment with PC-1.0 derived exosome and Western blot assay were performed to validate STARD13 as a target of exosomal miR-125b-5p in pancreatic cancer. Key findings: PC-1.0 derived exosomes promoted the migration and invasion of weakly invasive PC-1 cells. miRNA sequencing revealed 62 miRNAs upregulated in PC-1.0 derived exosomes. miR-125b-5p most significantly promoted migration and invasion and was associated with metastasis in pancreatic cancer. Further, miR-125b-5p was upregulated in highly invasive pancreatic cancer cells and increased migration, invasion, and EMT. Moreover, its upregulation was associated with activation of MEK2/ERK2 signaling. The tumor suppressor STARD13 was directly targeted by miR-125b-5p in pancreatic cancer, which was associated with good prognosis and was suppressed by exosomes derived from highly invasive cancer cells. Significance: This study explored the pro-metastatic role of exosomes derived from highly invasive pancreatic cancer cells and the associated aberrant expression of exosomal miRNAs, which may help to elucidate the metastatic mechanism of pancreatic cancer.
Significance
This study explored the pro-metastatic role of exosomes derived from highly invasive pancreatic cancer cells and the associated aberrant expression of exosomal miRNAs, which may help to elucidate the metastatic mechanism of pancreatic cancer.