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

• DOI: 10.1002/gcc.20580
• Publication Date: 2008-06-02T17:21:58Z
• Authors: Raquel Díaz; Javier Silva; José M. García; Yolanda Lorenzo; Vanesa García; Cristina Peña; Rufo Rodríguez; Concepción Muñoz; Fernando García; Félix Bonilla; Gemma Domínguez
• Keywords: EGF Family of Proteins; 0303 health sciences; Gene Expression Profiling; Calcium-Binding Proteins; Loss of Heterozygosity; Endothelial Growth Factors; Survival Analysis; 3. Good health; Gene Expression Regulation, Neoplastic; MicroRNAs; 03 medical and health sciences; Cell Line, Tumor; Colonic Neoplasms; Humans; RNA, Neoplasm

AbstractMicroRNAs (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 ofmiR‐17‐5p,miR‐106a, andmiR‐126on survival and its correlation with the levels of their target mRNAs and host gene andTP53alterations. We assessed in 110 colon cancer patients the levels ofmiR‐17‐5p,miR‐106a,miR‐126,E2F1, andEGFL7by quantitative real‐time RT‐PCR and loss of heterozygosity (LOH) in theTP53region. Tumor characteristics, disease‐free survival (DFS), and overall survival (OS) were examined in each patient. Altered expression ofmiR‐17‐5p,miR‐106a, andEGFL7was associated with pathological tumor features of poor prognosis. Downregulation ofmiR‐106apredicted shortened DFS (P= 0.03) and OS (P= 0.04).miR‐17‐5pcorrelated with DFS only at early stages (P= 0.07). Inverse correlations were found betweenmiR‐17‐5pandmiR‐106alevels and their target expression,E2F1(P= 0.04 andP= 0.03, respectively). No correlation was found betweenmiR‐126expression and its host gene levels,EGFL7.miR‐106aderegulation was revealed as a marker of DFS and OS independent of tumor stage. The lack of association between expression ofmiR‐126and its host geneEGFL7suggests their regulation by independent stimuli. Inverse correlation betweenmiR‐17‐5pandmiR‐106aandE2F1levels supportsE2F1as a target mRNA for the two miRNAs. © 2008 Wiley‐Liss, Inc.