Abstract 4186: miR-218 suppresses invasion and migration via inhibition of ZEB2 and N-Cadherin in colon cancer.

Abstract

Abstract The great majority of cancer deaths are due to metastasis. A hallmark of cancer metastasis is the process of epithelial to mesenchymal transition (EMT), in which cells alter their gene expression program resulting in loss of their epithelial characteristics and gain of typical mesenchymal properties. Recently, microRNAs have been shown to play key roles in the dynamic process of EMT, orchestrating a coordinated multi-target repression of genes and, together with master transcription factors, act in regulatory networks to alter cell function. We used a miRNA-microarray platform to identify differentially expressed microRNA genes in primary tumor, distant metastatic and corresponding normal samples in a cohort of resected patient tissues. From our list of differentially regulated microRNAs we focused on miR-218 as so far very little information has been accumulated regarding its function in cancer. In our microarray analysis, miR-218 was significantly downregulated in tumor/metastatic tissue compared to normal colon tissue. We validated miR-218 expression in an additional series of 42 colorectal cancer patient tissues, where we found a significant downregulation of miR-218 in tumor as compared to the corresponding normal tissues in over 80% of cases. Furthermore, ectopic expression of miR-218 significantly reduced in vitro invasion and migration of invasive colorectal cancer cell lines and upregulated the key epithelial marker E-cadherin, while silencing of miR-218 lead to enhanced migration and invasion. In addition, we identified two novel miR-218 target genes that are associated with EMT including ZEB2, a zinc-finger transcription factor, and N-Cadherin, using reporter gene, RT-PCR and Western blot analysis. In our present study, we show that miR-218 is a direct suppressor of EMT by its ability to downregulate ZEB2 and N-Cadherin expression and represents an additional molecule contributing to the complexity of the EMT regulatory network. Citation Format: Jasmin Batliner, Mohammed Abba, Christine Hauser, Heike Allgayer. miR-218 suppresses invasion and migration via inhibition of ZEB2 and N-Cadherin in colon cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4186. doi:10.1158/1538-7445.AM2013-4186