Tumor-suppressive microRNA-145 targets catenin δ-1 to regulate Wnt/β-catenin signaling in human colon cancer cells.

The constitutive activation of Wnt/β-catenin signaling plays a central role in colon cancer. MiR-145 was earlier identified as one of the microRNAs (miRNAs) down-regulated in colon cancer cells. However, the role of miR-145 in the Wnt/β-catenin signaling pathway is poorly understood. Here, we demonstrated that miR-145 played a pivotal role in the Wnt/β-catenin signaling pathway by perturbing the intracellular translocation of β-catenin in human colon cancer cells. The ectopic expression of miR-145 inhibited the growth of DLD-1 cells by disturbing β-catenin translocation into the nucleus, thereby leading to the down-regulation of LEF/TCF transcriptional target genes c-Myc and CyclinD1. We further demonstrated that miR-145 directly targeted catenin δ-1, contributing to the aberrant translocation of β-catenin through impaired nuclear shuttling with p21-activated kinase 4 (PAK4). These findings uncover a novel role of miR-145 in modulating intracellular translocation of β-catenin on Wnt/β-catenin signaling pathway.