Publication details
Correlation of selected microRNAs with histopathologic features of colorectal cancer
| Authors | |
|---|---|
| Year of publication | 2007 |
| Type | Article in Proceedings |
| Conference | ANALYTICAL CYTOMETRY IV. BOOK OF ABSTRACTS. |
| MU Faculty or unit | |
| Citation | |
| Field | Oncology and hematology |
| Keywords | colorectal cancer; patogenesis; microRNA |
| Description | PURPOSE: MicroRNAs (miRNAs) are endogenously expressed regulatory non-coding RNAs, 18 to 25 nucleotides in length, that repress protein translation through binding to target mRNAs. miRNAs have been implicated in many cellular processes including cell proliferation, differentiation and apoptosis. Although the number of verified human miRNA is still expanding, only few have been functionally described. However, emerging evidences suggest the potential 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). PATIENTS AND METHODS: In our study, we examined by real-time PCR expression levels of miR21, miR31, miR143, miR145 and let7a1 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 tissue was analyzed. MiRNAs expression levels were correlated with tumor stage, grade, size, anatomical localization and serum CEA levels. For data normalization we tried different approaches (18S rRNA, GAPDH, let7a1), but finally variability of let7a1 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, miR21 (p=0,0001) and miR31 (p=0,0006) were up-regulated and miR143 (p=0,013) and miR145 (p=0,018) were downregulated in tumors. MiR21 was also correlated with CRC stage. Although the highest levels of miR143 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 upregulation of miR31 (p=0,024) expression. Higher serum levels of CEA were associated with down-regulation of miR145 (p=0,05). We have not associated any of studied miRNAs to tumor grade and tumor size. Tumors with down-regulated miR143 and miR145 were bigger and more frequent (not significantly) in proximal colon. CONCLUSIONS: Our results suggest possible roles of miR21, miR31, miR143 and miR145 in colorectal cancer pathogenesis and different histopathologic phenotypes. This work was supported by IGA MZ CR NR/9076-4 |