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.

TAp73 variants largely mimic p53 suppressor activities, while DeltaTAp73 forms act as oncogenes through the inactivation of p53 and TAp73. The present study analysed how TAp73 and DeltaTAp73 levels might be affected by the presence of a 73 bp deletion in a regulatory region of p73. The clinical relevance of this deletion was also examined. ZEB1 can bind to the region repressing p73 transcription in vitro. The relationship between ZEB1 and p73 variant expression levels was studied in the context of this deletion and the levels of the ZEB1 cofactors p300 and CtBP. Tumour and normal tissue from 81 colorectal cancer patients was analysed to evaluate firstly the levels of TAp73, DeltaTAp73 (DeltaEx2p73, DeltaEx2/3p73, and DeltaNp73), ZEB1, p300, and CtBP by quantitative real-time RT-PCR, and secondly the presence of the 73 bp deletion. Tumour characteristics were examined in each patient. Suppressor and oncogenic isoforms of p73 were co-up-regulated in tumour tissues. Overexpression of p73 variants was associated with adverse tumour features. The 73 bp deletion was present in 40% of the patients and was associated with adverse pathological parameters of the tumours and also with TAp73 down-regulation. In those cases harbouring the deletion, the levels of ZEB1 and those of DeltaEx2p73, DeltaEx2/3p73, and DeltaNp73 correlated directly. Variations in the concentration of p300 affected the observed correlations between ZEB1 and the different p73 variants. In conclusion, in colorectal cancer, the 73 bp deletion in the first intron of the p73 gene and different expression levels of ZEB1 and p300 may act in concert to affect the ratio of TAp73/DeltaTAp73 forms, favouring p73 oncogenic variants. In addition, up-regulation of p73 oncogenic isoforms predicts a poor prognosis based on its relationship with advanced tumour stage.