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Deregulated expression of miR-106a predicts survival in human colon cancer patients

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Abstract

MicroRNAs (miRNAs) are noncoding RNAs that regulate expression of target mRNAs and are controlled by tumor suppressors and oncogenes. Altered expression of specific miRNAs in several tumor types and its association with poor prognosis parameters have been reported. Fewer data are available on its impact on patients' survival. We studied the impact of the expression of miR-17-5p, miR-106a, and miR-126 on survival and its correlation with the levels of their target mRNAs and host gene and TP53 alterations. We assessed in 110 colon cancer patients the levels of miR-17-5p, miR-106a, miR-126, E2F1, and EGFL7 by quantitative real-time RT-PCR and loss of heterozygosity (LOH) in the TP53 region. Tumor characteristics, disease-free survival (DFS), and overall survival (OS) were examined in each patient. Altered expression of miR-17-5p, miR-106a, and EGFL7 was associated with pathological tumor features of poor prognosis. Downregulation of miR-106a predicted shortened DFS (P = 0.03) and OS (P = 0.04). miR-17-5p correlated with DFS only at early stages (P = 0.07). Inverse correlations were found between miR-17-5p and miR-106a levels and their target expression, E2F1 (P = 0.04 and P = 0.03, respectively). No correlation was found between miR-126 expression and its host gene levels, EGFL7. miR-106a deregulation was revealed as a marker of DFS and OS independent of tumor stage. The lack of association between expression of miR-126 and its host gene EGFL7 suggests their regulation by independent stimuli. Inverse correlation between miR-17-5p and miR-106a and E2F1 levels supports E2F1 as a target mRNA for the two miRNAs. © 2008 Wiley-Liss, Inc.

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