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Clinical correlations of miR-21 expression in colorectal cancer patients and effects of its inhibition on DLD1 colon cancer cells

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

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.

Methods

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.

Results

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).

Conclusion

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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Acknowledgments

This study was supported by the Internal Grant Agency of Czech Ministry of Health NS 9814-4/2008, Czech Science Foundation (301/09/1115), and by the institutional research plan of Ministry of Health MZ0MOU2005, by The Ministry of Education, Youth and Sports for the project BBMRI CZ (LM2010004), and by the project “CEITEC – Central European Institute of Technology” (CZ.1.05/1.1.00/02.0068).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53, Brno, Czech Republic

    Petra Faltejskova, Andrej Besse, Marek Svoboda, Igor Kiss, Rostislav Vyzula & Ondrej Slaby

  2. Central European Institute of Technology, Masaryk University, Kamenice 5, Brno, Czech Republic

    Petra Faltejskova & Ondrej Slaby

  3. Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, Brno, Czech Republic

    Sabina Sevcikova & Lenka Kubiczkova

  4. Department of Experimental Biology, Faculty of Science, Masaryk University, Kamenice 5, Brno, Czech Republic

    Jan Smarda

Authors
  1. Petra Faltejskova
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  2. Andrej Besse
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  3. Sabina Sevcikova
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  4. Lenka Kubiczkova
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  5. Marek Svoboda
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  6. Jan Smarda
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  7. Igor Kiss
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  8. Rostislav Vyzula
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  9. Ondrej Slaby
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Corresponding author

Correspondence to Ondrej Slaby.

Additional information

Faltejskova Petra and Besse Andrej contributed equally to this work.

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Faltejskova, P., Besse, A., Sevcikova, S. et al. Clinical correlations of miR-21 expression in colorectal cancer patients and effects of its inhibition on DLD1 colon cancer cells. Int J Colorectal Dis 27, 1401–1408 (2012). https://doi.org/10.1007/s00384-012-1461-3

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  • DOI: https://doi.org/10.1007/s00384-012-1461-3

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