Single nucleotide polymorphisms in microRNA binding sites: implications in colorectal cancer.
Single nucleotide polymorphisms in microRNA binding sites: implications in colorectal cancer.
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MicroRNA结合位点中的单核苷酸多态性：大肠癌的影响。
DOI：
10.1155/2014/547154
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发表时间：
2014
影响因子：
--
通讯作者：
Purohit R
中科院分区：
文献类型：
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作者：
Bhaumik P;Gopalakrishnan C;Kamaraj B;Purohit R
癌症是一种复杂的遗传疾病，其特征是细胞增殖不受控制，由癌基因和肿瘤抑制基因的表达改变引起。当细胞增殖与结肠有关时，称为结直肠癌。大多数结直肠癌致癌基因都是miRNA(MicroRNA)的潜在靶点，它与mRNA的3‘非翻译区(UTR)结合并抑制翻译。发生在miRNA结合区的突变可以改变miRNA和mRNA的组合，并可以极大地改变基因的表达。我们推测miRNA结合位点的3‘非编码区突变可以改变miRNA与mRNA的相互作用，从而改变基因的表达。基因表达活性改变可促进结肠肿瘤的发生。因此，我们制定了一个系统的In Silico程序，整合了来自各种数据库的数据，遵循严格的选择标准，并确定了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到突变影响的潜在组织，丰富分析以发现基因的代谢功能，以及网络分析以突出致癌基因与其他基因的重要相互作用，以洞察复杂的网络将在突变时受到干扰。我们在电子计算机上提供了这些突变在结直肠癌中作用的证据。
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.