miR-381 functions as a tumor suppressor by targeting ETS1 in pancreatic cancer

Increasing evidence shows that microRNA (miR)-381 is involved in the carcinogenesis and biologic progression of various types of cancer in humans. However, its potential biologic role and mechanism in pancreatic cancer remain to be elucidated. In the present study, the expression and functional role of miR-381 in pancreatic cancer were investigated. It was found that miR-381 was significantly downregulated in pancreatic cancer tissues and cell lines. The biological functions of miR-381 were examined by measuring cell proliferation, migration, invasion and apoptosis in vitro and in vivo. The miR-381 target gene and signaling pathway were identified by luciferase activity assay and western blot assay. In vitro experiments confirmed that the enforced expression of miR-381 markedly suppressed cell proliferation, migration and invasion, and induced apoptosis in pancreatic cancer cells. By contrast, silencing the expression of miR-381 had the opposite effect. In addition, miR-381 inhibited xenograft tumor growth in vivo. Furthermore, ETS1 was identified as a direct target of miR-381, and western blot analysis showed that miR-381 negatively modulated the expression of ETS1. It was also demonstrated that miR-381 serves a key role in pancreatic cancer cells through regulating the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway. In conclusion, the data obtained suggested that miR-381 mediated cell proliferation, migration and invasion by targeting ETS1, partly through PI3K/AKT/mTOR signaling pathway. These results provide novel insights into understanding the potential effects and molecular mechanism of miR-381 on pancreatic cancer. miR-381 may serve as a novel potential marker for pancreatic cancer treatment in the future.