Single nucleotide polymorphisms in microRNA binding sites: implications in colorectal cancer.

Abstract

Cancer is a complex genetic disorder, characterised by uncontrolled cell proliferation and caused by altered expression of oncogenes and tumour suppressor genes. When cell proliferation pertains to colon, it is called colorectal cancer. Most of colorectal cancer causing genes are potential targets for the miRNA (microRNA) that bind to 3′UTR (untranslated regions) of mRNA and inhibit translation. Mutations occurring in miRNA binding regions can alter the miRNA, mRNA combination, and can alter gene expression drastically. We hypothesized that 3′UTR mutation in miRNA binding site could alter the miRNA, mRNA interaction, thereby altering gene expression. Altered gene expression activity could promote tumorigenesis in colon. Therefore, we formulated a systematic in silico procedure that integrates data from various databases, followed rigorous selection criteria, and identified mutations that might alter the expression levels of cancer causing genes. Further we performed expression analysis to shed light on the potential tissues that might be affected by mutation, enrichment analysis to find the metabolic functions of the gene, and network analysis to highlight the important interactions of cancer causing genes with other genes to provide insight that complex network will be disturbed upon mutation. We provide in silico evidence for the effect of these mutations in colorectal cancer.