Journal
INTERNATIONAL JOURNAL OF COLORECTAL DISEASE
Volume 27, Issue 11, Pages 1401-1408Publisher
SPRINGER
DOI: 10.1007/s00384-012-1461-3
Keywords
miR-21; Colorectal cancer; DLD-1; 5-FU; SN38; L-OHP; Sensitivity; Apoptosis; Migration
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Funding
- Internal Grant Agency of Czech Ministry of Health [NS 9814-4/2008]
- Czech Science Foundation [301/09/1115]
- Ministry of Health [MZ0MOU2005]
- Ministry of Education, Youth and Sports for the project BBMRI CZ [LM2010004]
- project CEITEC - Central European Institute of Technology [CZ.1.05/1.1.00/02.0068]
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MicroRNA-21 (miR-21) is one of the miRNAs that are frequently and highly overexpressed in tumor tissue of colorectal cancer (CRC) patients; however, only a little is known about its functional role in CRC. We examined the expression level of miR-21 in 44 paired samples of tumoral and non-tumoral colon tissues diagnosed for CRC using TaqMan real-time PCR method. Furthermore, we used miR-21 inhibitor (anti-miR-21) to transient knockdown of miR-21 in DLD-1 colon cancer cells and examined the effects of miR-21 silencing on viability, apoptosis, chemosensitivity, cell cycle, and migration of DLD1 cells. The expression levels of miR-21 were significantly increased in CRC tumor tissue (P < 0.0001). Significant differences in miR-21 levels were observed also between CRC tissues of patients with CRC in different clinical stages: I vs. II (P = 0.033) and I vs. IV (P = 0.021). Kaplan-Meier analysis proved that the miR-21 expression levels are correlated to shorter overall survival of CRC patients (P = 0.0341). MiR-21 silencing in DLD1 cell line had no effect on the cell viability; however, when combined with chemotherapeutics (5-FU, L-OHP, and SN38), it contributed to the decrease of cell viability. Suppression of miR-21 decreased cell migration ability of DLD-1 cells by nearly 30 % (P = 0.016). We have confirmed the overexpression of miR-21 in CRC samples and its correlation with advanced disease and shorter overall survival. These findings could be described in part by the fact that CRC cells with increased expression of miR-21 have higher migration ability.
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