Identification of functional genetic variants in miRNA binding site in genes associated with lung cancer

Anju Gupta, P. Kumari, Mottadi Shiva, Y. Hasija
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Abstract

The miRNAs are 22-46 nucleotidelong, non-protein coding RNAsthat act as oncogenes. Their altered expression can cause diseases, includingcancer. Lung cancer is causing death of million peopleworldwide. Yet only few genetic biomarkers are known for detecting lung cancer. miRNAs are those non-coding RNAs that act as such biomarkers. They act as oncogenes and regulate many biological processesand cellular pathways. The miRNAs regulate gene expression of protein coding genes by generating either translation repression or RNAdegradation. When they bind with 3' UTR of newly formed miRNA transcripts along with other helper proteins, they inhibit their expression and function. This translation inhibition, affects tumor suppressor genes and leads to cancer.miRNAexpression deregulation found in various cancers such as Prostrate, Breast, Colonialand Lung canceretc. In this study insilico approach has been used to find out functional genetic variation in miRNA binding sites of genes responsible for causing lung cancer. As a result of this study we have found 7 SNPs involved in such cancers-rs6772, rs1036672, rs739442, rs1050700, rs3185695, rs12723035, rs3787030. These SNPs can act as candidate biomarkers for lung cancer.
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肺癌相关基因miRNA结合位点功能基因变异的鉴定
mirna是22-46核苷酸长的非蛋白编码rna,作为癌基因。它们的表达改变会导致包括癌症在内的疾病。肺癌在全世界造成数百万人死亡。然而,目前已知能够检测肺癌的基因生物标志物很少。mirna是那些作为生物标记物的非编码rna。它们作为致癌基因,调节许多生物过程和细胞途径。mirna通过产生翻译抑制或rna降解来调节蛋白质编码基因的基因表达。当它们与新形成的miRNA转录本的3' UTR结合时,它们与其他辅助蛋白结合,抑制其表达和功能。这种翻译抑制作用影响肿瘤抑制基因并导致癌症。在前列腺癌、乳腺癌、结肠癌和肺癌等多种癌症中发现mirna表达失调。本研究采用insilico方法发现了导致肺癌的基因miRNA结合位点的功能性遗传变异。通过这项研究,我们发现了7个与这些癌症相关的snp -rs6772, rs1036672, rs739442, rs1050700, rs3185695, rs12723035, rs3787030。这些snp可以作为肺癌的候选生物标志物。
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