Pancreatic cancer-associated fibroblasts express tumor-suppressive microRNAs

Cancer-associated fibroblast (CAF) is abundant in the tumor microenvironment (TME) and broadly accepted as an oncogenic component for pancreatic ductal adenocarcinoma (PDAC). We previously reported a tumor-suppressive role of CAFs via a CAF-specific miRNA that can be efficiently transferred via exosomes within the TME and inhibit PDAC cell growth. In this study, we expanded our search and found several differentially expressed miRNAs within CAFs (CAF-DE-miRNAs) including the most elevated miR-145-5p and miR-199a-5p. These miRNAs exhibit tumor-suppressive roles likely via complex regulation of several signaling proteins within the TGF-β and EGFR (ErbB) signaling pathways. Our study indicates a more complex role of CAFs within the TME and provides a distinct mechanism of CAF-mediated tumor suppression.