Abstract 4172: MiR-215 expression in tumor tissue and in vitro effects of its replacement in colorectal cancer.

Abstract

Abstract Background: MicroRNAs (miRNAs) constitute a robust regulatory network with post-transcriptional regulatory efficiency for almost one half of human coding genes, including oncogenes and tumor suppressors. Methods: We determined the expression profile of 667 miRNAs in colorectal cancer (CRC) tissues and paired non-tumoral tissues and identified 42 differentially expressed miRNAs. One of the most significantly altered miRNAs was miR-215, significantly down-regulated in tumor tissue. We chose miR-215 for further validation on an independent cohort of 125 clinically characterized CRC patients and for in vitro functional studies on DLD1, HCT116 and HT29 cell lines. Results: MiR-215 was proved to be significantly decreased in CRC tumor tissues (p<0.0001) and to be negatively correlated with clinical stage (p<0.0001) and tumor grade (p=0.04). In vitro analyses showed that ectopic expression of miR 215 decreases viability in DLD1 (p=0.05) and HCT116 (p=0,05) cells, increases apoptosis in HCT116 (p=0.005), promotes cell cycle arrest (inhibited G1/S transition) in HCT-116 colon cancer cells (p=0.01) and decreases migration in DLD1 (p=0.05) and HT-29 cells (p=0.05). We further confirmed transcription factor HOXB9 as direct target of miR-215 on the mRNA and protein level. Conclusions: These findings indicate that miR 215 play an important role in CRC as tumor suppressor and contributes to CRC pathogenesis. Supported by Internal Grant Agency of Czech Ministry of Health, grant numbers: NT13549-4/2012 a NT13860 4/2012. Citation Format: Petra Faltejskova, Marek Svoboda, Jitka Mlcochova, Klara Srutova, Pavel Fabian, Rostislav Vyzula, Ondrej Slaby. MiR-215 expression in tumor tissue and in vitro effects of its replacement in colorectal 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 4172. doi:10.1158/1538-7445.AM2013-4172