MiR-377-3p suppresses colorectal cancer through negative regulation on Wnt/β-catenin signaling by targeting XIAP and ZEB2

Abstract

Aberrant activation of Wnt/β-catenin signaling is a common event in the development of colorectal cancer (CRC). It is important to identify new molecules and mechanisms that can negatively regulate Wnt/β-catenin signaling. MicroRNAs are considered as promising candidates for cancer diagnosis and therapy. In our study, we found that miR-377-3p was significantly decreased in CRC samples compared to the normal mucosa tissues, especially in the patients at stage III/IV. Functional studies showed that overexpression of miR-377-3p suppressed and silence of miR-377-3p enhanced the proliferation, migration and chemoresistance of CRC cells. Molecularly, miR-377-3p inhibited Wnt/β-catenin signaling by directly targeting ZEB2 and XIAP, which were the positive regulators of Wnt/β-catenin signaling. Overexpression of ZEB2/XIAP could counteract the tumor suppressing phenotypes induced by miR-377-3p. Therefore, we uncovered the anti-cancer role and the relevant mechanisms of miR-377-3p in CRC, which might provide novel targets for designing new anti-tumor strategies.

Keywords: Colorectal cancer; MiR-377-3p; XIAP; ZEB2; β-catenin.