High expression of microRNA-4295 contributes to cell proliferation and invasion of pancreatic ductal adenocarcinoma by the down-regulation of Glypican-5

Highlights: • GPC5 expression is decreased in PDAC. • GPC5 inhibits cell proliferation and the invasion of PDAC cells. • GPC5 is involved in regulating Wnt/β-catenin signaling in PDAC cells. • GPC5 is targeted and regulated by miR-4295 in PDAC cells. A growing amount of evidence has documented that Glypican-5 (GPC5) is an important regulator of tumor progression. However, little is known about the role of GPC5 in pancreatic ductal adenocarcinoma (PDAC). In this study, we aimed to investigate the potential function and regulatory mechanism of GPC5 in PDAC. We found that GPC5 expression was significantly down-regulated in PDAC cell lines. The overexpression of GPC5 inhibited cell proliferation and the invasion of PDAC cells. In addition, the overexpression of GPC5 suppressed Wnt/β-catenin signaling in PDAC cells. Bioinformatic analysis predicted that GPC5 was a target gene of microRNA-4295 (miR-4295). The inhibition of miR-4295 significantly up-regulated the expression of GPC5. Moreover, the inhibition of miR-4295 inhibited the proliferation, invasion and Wnt/β-catenin signaling in PDAC cells. Notably, the knockdown of GPC5 partially reversed the anti-tumor effect of miR-4295 inhibition. Taken together, our results suggest GPC5 as a tumor suppressor in PDAC and its expression is possibly regulated by miR-4295. Our study indicates that the miR-4295/GPC5 axis may play an important role in the pathogenesis of PADC and has potential applications for the development of PDAC therapy.