MicroRNA-520e targets AEG-1 to suppress the proliferation and invasion of colorectal cancer cells through Wnt/GSK-3β/β-catenin signalling.

Abstract

MicroRNA-520e (miR-520e) is increasingly being recognized as a cancer-related miRNA in multiple cancer types; however, little is known about its role in colorectal cancer. In this study, we determined the specific role of miR-520e in colorectal cancer. Expression of miR-520e was lower in colorectal cancer tissues compared to normal tissues. Overexpression of miR-520e significantly decreased the proliferation, colony formation and invasion of colorectal cancer cells, while inhibition of miR-520e exhibited the opposite effect. Moreover, miR-520e was found to target the 3'-untranslated region of astrocyte elevated gene-1 (AEG-1) and inhibit AEG-1 expression in colorectal cancer cells. An inverse correlation between miR-520e and AEG-1 expression was confirmed in colorectal cancer tissues. Notably, miR-520e suppressed the phosphorylation of glycogen synthase kinase-3β and decreased the expression of β-catenin, leading to inactivation of Wnt/β-catenin signalling in colorectal cells. A rescue assay confirmed that miR-520e regulates cell proliferation, invasion and Wnt/β-catenin signalling through targeting AEG-1. Taken together, these results indicate that miR-520e plays a critical role in regulating colorectal cancer cell proliferation and invasion by inhibiting Wnt/β-catenin signalling via AEG-1. Our study highlights the importance of the miR-520e/AEG-1/Wnt/β-catenin signalling axis in colorectal cancer, thus targeting miR-520e may represent an effective therapeutic strategy.