Identification and analysis of oncogenic non-synonymous single nucleotide polymorphisms in the human NRAS gene: An exclusive in silico study

IF 3.5 Q3 Biochemistry, Genetics and Molecular Biology
Md. Mozibullah , Hadieh Eslampanah Seyedi , Marina Khatun , Md Solayman
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引用次数: 0

Abstract

Background

N-ras protein is encoded by the NRAS gene and operates as GDP-GTP-controlled on/off switching. N-ras interacts with cellular signaling networks that regulate various cellular activities including cell proliferation and survival. The nonsynonymous single nucleotide polymorphism (nsSNPs)-mediated alteration can substantially disrupt the structure and activity of the corresponding protein. N-ras has been reported to be associated with numerous diseases including cancers due to the nsSNPs. A comprehensive study on the NRAS gene to unveil the potentially damaging and oncogenic nsSNPs is yet to be accomplished. Hence, this extensive in silico study is intended to identify the disease-associated, specifically oncogenic nsSNPs of the NRAS gene.

Results

Out of 140 missense variants, 7 nsSNPs (I55R, G60E, G60R, Y64D, L79F, D119G, and V152F) were identified to be damaging utilizing 10 computational tools that works based on different algorithms with high accuracy. Among those, G60E, G60R, and D119G variants were further filtered considering their location in the highly conserved region and later identified as oncogenic variants. Interestingly, G60E and G60R variants were revealed to be particularly associated with lung adenocarcinoma, rhabdomyosarcoma, and prostate adenocarcinoma. Therefore, D119G could be subjected to detailed investigation for identifying its association with specific cancer.

Conclusion

This in silico study identified the deleterious and oncogenic missense variants of the human NRAS gene that could be utilized for designing further experimental investigation. The outcomes of this study would be worthwhile in future research for developing personalized medicine.

鉴定和分析人类 NRAS 基因中的致癌非同义单核苷酸多态性:独有的硅学研究
背景N-ras蛋白由NRAS基因编码,以GDP-GTP控制的开关方式运行。N-ras 与调节细胞增殖和存活等各种细胞活动的细胞信号网络相互作用。非同义单核苷酸多态性(nsSNPs)介导的改变会极大地破坏相应蛋白质的结构和活性。据报道,N-ras 与许多疾病(包括癌症)有关,原因就在于 nsSNPs。目前尚未完成对 NRAS 基因的全面研究,以揭示具有潜在破坏性和致癌性的 nsSNPs。结果在 140 个错义变异中,有 7 个 nsSNPs(I55R、G60E、G60R、Y64D、L79F、D119G 和 V152F)利用 10 种基于不同算法的计算工具被高精度地鉴定为具有损伤性。其中,G60E、G60R 和 D119G 变体因位于高保守区而被进一步筛选,随后被确定为致癌变体。有趣的是,G60E 和 G60R 变体被发现与肺腺癌、横纹肌肉瘤和前列腺癌特别相关。因此,可以对 D119G 进行详细调查,以确定其与特定癌症的关系。 结论这项默克研究确定了人类 NRAS 基因的有害和致癌错义变异,可用于设计进一步的实验研究。这项研究的成果值得在未来的研究中用于开发个性化药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Genetic Engineering and Biotechnology
Journal of Genetic Engineering and Biotechnology Biochemistry, Genetics and Molecular Biology-Biotechnology
CiteScore
5.70
自引率
5.70%
发文量
159
审稿时长
16 weeks
期刊介绍: Journal of genetic engineering and biotechnology is devoted to rapid publication of full-length research papers that leads to significant contribution in advancing knowledge in genetic engineering and biotechnology and provide novel perspectives in this research area. JGEB includes all major themes related to genetic engineering and recombinant DNA. The area of interest of JGEB includes but not restricted to: •Plant genetics •Animal genetics •Bacterial enzymes •Agricultural Biotechnology, •Biochemistry, •Biophysics, •Bioinformatics, •Environmental Biotechnology, •Industrial Biotechnology, •Microbial biotechnology, •Medical Biotechnology, •Bioenergy, Biosafety, •Biosecurity, •Bioethics, •GMOS, •Genomic, •Proteomic JGEB accepts
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