Publication details
Association of miR-21, miR-31, miR-143, miR-145 and let-7a-1 levels with histopathologic features of colorectal cancer
| Authors | |
|---|---|
| Year of publication | 2007 |
| Type | Article in Periodical |
| Magazine / Source | European Journal of Cancer |
| MU Faculty or unit | |
| Citation | |
| Field | Oncology and hematology |
| Keywords | colorectal cancer; microRNA; pathogenesis; metastasis |
| Description | RNAs, that repress protein translation through binding to target mRNAs. Although the number of verified human miRNA 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 studies, mainly based on microarrays technology applied on colorectal cancer cell lines, showed altered expression levels of several miRNAs in colorectal cancer (CRC). MATERIALS AND METHODS: In our study, we examined by Real-Time PCR expression levels of miR-21, miR-31, miR-143, miR-145 and let-7a-1 in bioptic samples of 29 colorectal cancer patients including 3 cases of IUCC Stage I, 11 of Stage II, 6 of Stage III, 9 of Stage IV. For 6 cases of CRC samples also adjacent non-tumor tissues were analyzed. MiRNAs expression levels were correlated with tumor stage, grade, size, anatomical localization, serum CEA levels and p53 protein expression in tumors. For data normalization we tried different approaches (18S rRNA, GAPDH, let-7a-1). Finally, variability of let-7a-1 expression was shown to be the lowest. P values were calculated using Mann-Whitney U test. RESULTS: Expression levels of all analyzed miRNAs significantly differ in tumor and normal mucosa, miR-21 (p=0,0001) and miR-31 (p=0,0006) were up-regulated and miR-143 (p=0,013) and miR-145 (p=0,018) were down-regulated in tumors. MiR-21 was also correlated with CRC stage. Although the highest levels of miR-143 and miR-145 were in normal mucosa, we identified positive correlation of tumor stage and their expression suggesting altered tumor suppressor function of these miRNAs in early events of colorectal carcinogenesis. Distal CRC showed significant up-regulation of miR-31 (p=0,024) expression. Higher serum levels of CEA were associated with down-regulation of miR-145 (p=0,05). Tumors with high expression of p53 protein had significantly lower expression of miR-143 (p=0,02). We have not associated any of studied miRNAs to tumor grade and tumor size. Tumors with down-regulated miR-143 and miR-145 were bigger and more frequent (not significantly) in proximal colon. CONCLUSIONS: Our results suggest possible roles of miR-21, miR-31, miR-143 and miR-145 in colorectal cancer pathogenesis and different histopathologic phenotypes. Supported by IGA MZ CR NR/9076 - 4 |