MiR-215 expression in tumor tissue and in vitro effects of itsreplacement in colorectal cancer

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.