MiRNA Genes Constitute New Targets for Microsatellite Instability in Colorectal Cancer

• DOI: 10.1371/journal.pone.0031862
• Publication Date: 2012-02-14T22:25:55Z
• Authors: Nizar El-Murr; Zoulira Abidi; Kristell Wanherdrick; Magali Svrcek; Marie-Pierre Gaub; Jean-François Fléjou; Richard Hamelin; Alex Duval; Thécla Lesuffleur
• Keywords: Microsatellite Instability

Mismatch repair-deficient colorectal cancers (CRC) display widespread instability at DNA microsatellite sequences (MSI). Although MSI has been reported to commonly occur coding repeats, leading alterations in the function of a number genes encoding cancer-related proteins, nothing is known about putative impact this process on non-coding microRNAs. In miRbase V15, we identified very few human microRNA with mono- or di-nucleotide repeats (n = 27). A mutational analysis these large series CRC cell lines and primary tumors underscored 15 24 successfully studied variable frequencies ranging from 2.5% 100%. Following maximum likelihood statistical method, were separated into two groups that differed significantly their mutation tendency represent mutations may not be under selective pressures during tumoral progression. The first group included 21 displayed no CRC. second contained three genes, i.e., hsa-mir-1273c, hsa-mir-1303 hsa-mir-567, frequent (≥80%) sometimes bi-allelic tumors. For only one expressed colonic tissues, hsa-mir-1303, direct link was found between presence levels mature miR expression lines, as determined by sequencing quantitative PCR respectively. Overall, our results provide evidence miRNA are relatively rare preserved due MMR-deficient cancer cells. Functional studies now required conclude whether mutated miRNAs, especially miR-1303, might have role tumorigenesis.