Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Cancer Med. 2020 Dec;9(24):9511-9528. doi: 10.1002/cam4.3546. Epub 2020 Oct 18.
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.
结直肠癌（CRC）和肥胖是临床相关的实体，它们的发展涉及一系列复杂的过程。microRNAs（miRNAs）通过调节 CRC 和肥胖相关基因参与这些过程。本研究旨在开发一种计算方法，系统地识别和优先考虑肥胖和 CRC 中 miRNA 靶位点多态性。使用全基因组关联研究（GWAS）的数据检索 CRC 和肥胖相关的变体。检索并使用一系列生物信息学分析优先考虑位于实验验证或计算预测 miRNA 靶位的多态性。我们发现了 6284 个 CRC 和 38931 个肥胖独特的变体。对于 CRC，有 33 个单倍型变体在 134 个相互作用中位于 miRNA 靶位，而对于肥胖，我们发现了超过 935 个独特的相互作用。功能优先化 SNP 表明，153 个肥胖和 50 个 CRC 独特相互作用中的 SNP 通过改变靶 RNA 二级结构对 miRNA:mRNA 整合具有破坏性影响。在肥胖和 CRC 中，分别有 418 个和 103 个独特相互作用的靶位结构可及性降低，有 516 个和 79 个独特相互作用的靶位结构可及性增加。对于肥胖和 CRC SNP 的影响，分别有 127 个和 17 个独特相互作用的 miRNA:mRNA 杂交稳定性增加，有 33 个和 24 个独特相互作用的 miRNA:mRNA 杂交稳定性降低。在这项研究中，15 个相互作用中有 7 个 SNP 和 4 个相互作用中有 3 个 SNP 被优先考虑用于肥胖和 CRC，这些 SNP 可用于未来的研究，以寻找 CRC 和肥胖诊断、预后或治疗的潜在生物标志物。
