MicroRNA-15a/16 regulate protein metabolism and are associated with clinical outcomes in pancreatic ductal adenocarcinoma.

Dysregulated cellular protein metabolism is a key hallmark of pancreatic ductal adenocarcinoma (PDAC). However, much remains to be learned about how this process is regulated in cancerous cells. Here we investigated the role of two co-transcribed microRNA (miRNA) species, miR-15a/16, in regulating cellular protein translation, cell growth, metabolic processes, and clinical features in PDAC. Using cultured PDAC models, we show that overexpression of miR-15a/16 in cancerous cells slows proliferation and attenuates protein synthesis rates. Bioinformatics analysis reveals that these miRNAs target a broad suite of pathophysiological and metabolic pathways, including numerous genes in cancer- and protein-related processes. Finally, using publicly available patient data, we report that miR-15a/16 expression is lower in PDAC tumors and in patients with pancreatitis than in healthy controls, and that high expression of miR-15a/16 in tumors is associated with improved survival in patients. Our results indicate that miR-15a/16 act as regulators of protein metabolism in PDAC, with potential clinical implications for the management of this devastating disease.