Differential miRNA-mRNA co-expression networks in colorectal cancer

Colorectal cancer (CRC) is one of the most common neoplasms in the world and its molecular biology is one of the most intensively and successfully studied. Altered expression of miRNAs is associated with the development and progression of CRC by regulating the translation of oncogenes and tumor suppressor genes (1). Moreover, miRNA-expression profiling has been exploited to predict the functions of the deregulated miRNAs by detecting the enriched pathways of their target genes. In cancer, genetic variants in miRNA genes and mRNA targets can alter miRNA-mediated repression (2). We studied changes in miRNA-mRNA CRC interactions in terms of differential co-expressions relative to normal condition. The aim was to capture alterations resulting from the aforementioned modifications that influence miRNA activity on gene transcription. By using paired miRNA-mRNA expression profiles, correlations between miRNA and gene expressions were estimated for both tumor and normal tissues. Correlation changes between the two conditions were incorporated into scores of predefined gene sets in order to identify signaling pathways and biological processes with an altered miRNA-mediated control. Compared with other types of miRNA-mRNA interaction scores, using co-expression coefficients with any a priori information has several advantages: a complete coverage of the human genes on the chip, little bias due to the knowledge obtained from the published literature, and the ability to infer condition specific relationships. Notably, our integrative analysis suggested an alteration in CRC tissues in the interplay between miRNAs and the eukaryotic translation initiation factor 3 (eIF3) which has a central role in recruiting both mRNAs and the cellular translation machinery to form translation initiation complexes (3). Unveiling differential miRNA-mRNA co-expression properties allows to gain insights into miRNA-mediated molecular mechanisms underlying the pathogenesis of the disease and may suggest novel drug targets to be validated. References: 1.Calin GA, Croce CM., MicroRNA signatures in human cancers. Nat Rev Cancer (2006);6:857-66. 2. Ryan BM, Robles AI, Harris CC., Genetic variation in microRNA networks: the implications for cancer research. Nature Reviews Cancer (2010); 389-402. 3. Jackson RJ, Hellen CU, Pestova TV, The mechanism of eukaryotic translation initiation and principles of its regulation. Nat Rev Mol Cell Biol (2010) 11:113-127.