Knockdown of oncogenic microRNA-21 displays cytotoxicity in p53 wild-type colon cancer cells
| Autoři | |
|---|---|
| Rok publikování | 2008 |
| Druh | Článek ve sborníku |
| Konference | European Journal of Cancer Supplements |
| Fakulta / Pracoviště MU | |
| Citace | |
| Obor | Onkologie a hematologie |
| Klíčová slova | colorectal; microRNAs |
| Popis | Although the number of verified human microRNAs (miRNAs) is still expanding, only few have been functionally described. However, emerging evidences suggest the involvement of altered regulation of miRNA in pathogenesis of cancers and these genes are thought to function as both tumours suppressor and oncogenes. Previous data suggest altered regulation of microRNA-21 (miR-21) expression in CRC. In our study, we examined by Real-Time PCR expression levels of microRNA-21 (miR-21) in 60 colorectal tumors and 40 paired adjacent non-tumor tissues and correlated them to selected clinicopathologic features and survival parameters. We used expression of U6 small nuclear RNA (RNU6B) for data normalization and standard ddCt method for relative quantification of miRNA expression. Levels of miR-21 were significantly higher in tumors comparing to normal mucosa (p < 0,0001, Wilcoxon matched-pairs test). High expression levels of miR-21 in tumors (based on high tertile) were associated also with a poor survival (long-rank p=0,043). Up-regulation of miR-21 was previously associated with high potential of invasion, intravasation and metastasis in pre-clinical colorectal cancer models. Till now no data exist focused on miR-21 effects on CRC cells proliferation. To elucidate potential involvement of miR-21 in regulation of colon cancer cells (DLD1, SW837, HCT116 wt-p53, HCT116 null-p53) proliferation we tested effects of synthetic 2'OMe-antisense-miR-21 (anti-miR-21) transfection (2'OMe-EGFP as control) on their growth by use of MTT test. Proliferation was not affected in a null-p53 cell line or cell lines expressing mutated p53 (DLD1, SW837). In a wild-type p53-expressing cell line we observed more than 20% decrease of cells proliferation by MTT test after transfection of anti-miR-21. Now we are testing attenuating effect of anti-miR-21 on CRC cells survival under conditions of p53-directed apoptosis induced by doxorubicin treatment. Simultaneously, we are evaluating also changes in invasive properties of anti-miR-21 transfected cancer cells by matrigel invasion assay. Our results suggest possible role of miR-21 in colorectal cancer pathogenesis. Supported by IGA MZ CR NR/9076-4 and project MZ0MOU2005 |