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微小RNA结合位点中的单核苷酸多态性:对结直肠癌的影响

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

作者信息

Bhaumik Panchalee, Gopalakrishnan Chandrasekhar, Kamaraj Balu, Purohit Rituraj

机构信息

School of Bio Sciences and Technology (SBST), Bioinformatics Division, Vellore Institute of Technology University, Vellore, Tamil Nadu 632014, India.

出版信息

ScientificWorldJournal. 2014;2014:547154. doi: 10.1155/2014/547154. Epub 2014 Dec 24.

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.

摘要

癌症是一种复杂的基因紊乱疾病,其特征为细胞不受控制地增殖,由癌基因和肿瘤抑制基因的表达改变所致。当细胞增殖发生在结肠时,就称为结直肠癌。大多数导致结直肠癌的基因都是微小RNA(miRNA)的潜在作用靶点,这些miRNA与信使核糖核酸(mRNA)的3'非翻译区(UTR)结合并抑制翻译。发生在miRNA结合区域的突变会改变miRNA与mRNA的结合,进而可能极大地改变基因表达。我们推测,miRNA结合位点的3'UTR突变可能会改变miRNA与mRNA的相互作用,从而改变基因表达。基因表达活性的改变可能会促进结肠肿瘤的发生。因此,我们制定了一个系统的计算机模拟流程,整合来自各种数据库的数据,遵循严格的筛选标准,识别可能改变致癌基因表达水平的突变。此外,我们进行了表达分析,以阐明可能受突变影响的潜在组织,进行了富集分析以找出基因的代谢功能,并进行了网络分析以突出致癌基因与其他基因之间的重要相互作用,从而深入了解突变时复杂网络将受到干扰的情况。我们提供了计算机模拟证据,证明这些突变在结直肠癌中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ce/4310495/e43e9a4ad1fc/TSWJ2014-547154.001.jpg

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