Mutations in MicroRNA Genes and Their Binding Sites are Infrequently Associated with Human Colorectal Cancer in the Kashmiri Population.

Abstract

MicroRNAs are small non-coding RNAs, 19-24 nucleotides in length that bind to the 3'UTR of target mRNAs and thus regulate gene expression post transcriptionally. MiRNAs have been implicated in various biological and pathological processes. The binding of miRNAs to 3'UTR is crucial for regulating the mRNA level and hence protein expression. The complementarity between the miRNA and its target mRNA is critical for the outcome of the miRNA mediated translational regulation. Changes in the nucleotide sequence of either the miRNA or its target binding site can deregulate gene expression and hence lead to the development of various pathological conditions, including tumorigenesis. To determine whether sequence alterations in miRNA genes and their target sites in mRNAs are associated with the colorectal cancers, we screened two miRNA genes-Let-7c, mir-206 and selected miRNA binding regions on KRAS, TP53 and GJA1 3'UTR. This study was carried out on 60 human colorectal cancer tissue samples. Our sequencing results did not reveal any mutation/single-nucleotide polymorphism in either the miRNAs or the miRNA binding sites in any of the tumor samples. This data suggests that mutations/SNPs targeting miRNA genes or their binding sites in 3'-untranslated regions are infrequent events in the development of colorectal cancer in Kashmiri population.