Background: We have previously shown that miR-215 suppressed the expression of key targets such as thymidylate synthase (TS), dihydrofolate reductase, and denticleless protein homolog (DTL) in colon cancer. miR-215 is a tumor suppressor candidate due to the upregulation of p53 and p21 by targeting DTL. However, high levels of miR-215 conferred chemoresistance due to cell cycle arrest and reduced cell proliferation by suppressing DTL. In this study, the clinical significance of miR-215 was further investigated as a potential prognostic biomarker in colon cancer patients.
Methods: Total RNAs were extracted from 34 paired normal and colon (stage II and III) tumor specimens using the Trizol-based approach. The levels of miR-215 and a closely related miR-192 were quantified using quantitative real-time polymerase chain reaction (qRT-PCR) expression analysis. The expression of DTL mRNA and protein were quantified by real time qRT-PCR and immunohistochemistry.
Results: The expression levels of miR-192 (P = .0008) and miR-215 (P < .0001) were significantly decreased in colon tumors compared with normal tissues. DTL was significantly over-expressed and was inversely correlated with miR-215, further suggesting an in vivo physiologic relevance of miR-215 mediated DTL suppression. Kaplan-Meier survival analysis by Cox regression revealed that high levels of miR-215 expression (hazard ratio, 3.516; 95% confidence interval, 1.007-12.28, P = .025) are closely associated with poor patient's overall survival. Furthermore, an elevated expression of a miR-215 target protein DTL was detected in colon cancer tissues whereas no expression was present in normal tissues.
Conclusion: miR-215 has a unique potential as a prognostic biomarker in stage II and III colon cancer.
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