The down-regulation of microRNA-137 contributes to the up-regulation of retinoblastoma cell proliferation and invasion by regulating COX-2/PGE2 signaling

Abstract

MicroRNA-137 (miR-137) plays an important role in the development and progression of many types of human cancers; however, the role of miR-137 in retinoblastoma (RB) remains unclear. In this study, we aimed to investigate the functional significance and molecular mechanisms of miR-137 in RB. We reported that miR-137 was frequently down-regulated in RB tissues and cell lines. The overexpression of miR-137 inhibited RB cell proliferation and invasion, while the suppression of miR-137 promoted RB cell proliferation and invasion. Bioinformatic analysis predicted that cyclooxygenase-2 (COX-2) was a potential target gene of miR-137, which was validated by a dual-luciferase reporter assay. Moreover, our results showed that miR-137 negatively regulated the expression of COX-2 and the production of prostaglandin E2 (PGE2) in RB cells. The knockdown of COX-2 suppressed the proliferation and invasion of RB cells as well as the production of PGE2. The overexpression of COX-2 significantly reversed the inhibitory effect of miR-137 overexpression on RB cell proliferation and invasion. Taken together, these results suggest that miR-137 suppresses the proliferation and invasion of RB cells by targeting COX-2/PGE2. Our study reveals a tumor suppressive role of miR-137 in the progression of RB and suggests miR-137 as a potentially effective therapeutic target for the treatment of RB.