Journal
CANCER LETTERS
Volume 335, Issue 2, Pages 332-342Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2013.02.060
Keywords
miR-145; Wnt/beta-catenin signaling; Catenin delta-1; Colon cancer
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Funding
- Ministry of Education, Science, Sports, and Culture of Japan
- Grants-in-Aid for Scientific Research [13J00639] Funding Source: KAKEN
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The constitutive activation of Wnt/beta-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/beta-catenin signaling pathway is poorly understood. Here, we demonstrated that miR-145 played a pivotal role in the Wnt/beta-catenin signaling pathway by perturbing the intracellular translocation of beta-catenin in human colon cancer cells. The ectopic expression of miR-145 inhibited the growth of DLD-1 cells by disturbing beta-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 delta-1, contributing to the aberrant translocation of beta-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 beta-catenin on Wnt/beta-catenin signaling pathway. (c) 2013 Elsevier Ireland Ltd. All rights reserved.
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