Down-regulation of miR-30a-5p is Associated with Poor Prognosis and Promotes Chemoresistance of Gemcitabine in Pancreatic Ductal Adenocarcinoma.

Abstract

MicroRNA-30a-5p (miR-30a-5p) plays an important role in many biological and pathological processes, and therefore has been studied extensively. However, its expression and function in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Furthermore, whether miR-30a-5p affects sensitivity of PDAC cells to gemcitabine (GEM) is worthy of further exploration. The results showed that miR-30a-5p expression in pancreatic cancer was decreased and the down-regulated expression correlated with poor prognosis, while up-regulating miR-30a-5p suppressed tumor cell proliferation, cell cycle and increased apoptosis. MiRNA expression profiles between gemcitabine-resistant pancreatic cancer cells and parental pancreatic cancer cells showed significant change of miR-30a-5p expression. Besides, up-regulating miR-30a-5p in PDAC significantly increased the chemosensitivity of gemcitabine. Furthermore, FOXD1 is a direct target of miR-30a-5p and the miR-30a-5p/FOXD1/ERK axis may play an important role in the development of gemcitabine resistance in pancreatic cancer. In summary, our study showed that miR-30a-5p increases the sensitivity of pancreatic cancer to gemcitabine, and it may be a potential therapeutic target to overcome gemcitabine resistance.