An in Silico Approach to Identify and Prioritize Mirnas Target Sites Polymorphisms in Colorectal Cancer and Obesity Publisher Pubmed



Gholami M^{1, 2} ; Zoughi M³ ; Larijani B² ; M Amoli M³ ; Bastami M⁴ Show Affiliations
Source: Cancer Medicine Published:2020

Abstract

Colorectal cancer (CRC) and obesity are linked clinical entities with a series of complex processes being engaged in their development. MicroRNAs (miRNAs) participate in these processes through regulating CRC and obesity-related genes. This study aimed to develop an in silico approach to systematically identify and prioritize miRNAs target sites polymorphisms in obesity and CRC. Data from genome-wide association studies (GWASs) were used to retrieve CRC and obesity-associated variants. The polymorphisms that were resided in experimentally verified or computationally predicted miRNA target sites were retrieved and prioritized using a range of bioinformatics analyses. We found 6284 CRC and 38931 obesity unique variants. For CRC 33 haplotypes variants in 134 interactions were in miRNA targetome, while for obesity we found more than 935 unique interactions. Functionally prioritized SNPs revealed that, SNPs in 153 obesity and 50 CRC unique interactions were have disruptive effects on miRNA:mRNA integration by changing on target RNA secondary structure. Structural accessibility of target sites were decreased in 418 and 103 unique interactions and increased in 516 and 79 interactions, for obesity and CRC, respectively. The miRNA:mRNA hybrid stability was increased in 127 and 17 unique interactions and decreased in 33 and 24 interactions for the effect of obesity and CRC SNPs, respectively. In this study, seven SNPs with 15 interactions and three SNPs with four interactions were prioritized for obesity and CRC, respectively. These SNPs could be used for future studies for finding potential biomarkers for diagnoses, prognosis, or treatment of CRC and obesity. © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.