一个in-silico研究通过评估SOCS3基因中编码和非编码非同义单核酸变体来确定对癌症的易感性
Sadri Fatemeh1, Zarei Mahboobeh1, Ahmadi Khadijeh2
1Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Journal of biomolecular structure & dynamics
|September 27, 2023
概括
这项研究确定了SOCS3基因中有害的单核酸变体 (SNV),这对抑制癌症至关重要. 这些发现突出了影响蛋白质功能和基因表达的特定SNV,有助于未来的癌症风险研究.
科学领域:
- 遗传学和分子生物学
- 癌症研究 癌症研究
- 生物信息学是一种生物信息学.
背景情况:
- 单核酸变体 (SNVs) 可以改变基因表达和蛋白质功能,导致癌症风险.
- SOCS3 (细胞因子信号传递3抑制剂) 是JAK/STAT通路中的关键瘤抑制剂,在癌症中经常被抑制.
- 了解SOCS3基因变异的影响对于癌症研究至关重要.
研究的目的:
- 在SOCS3基因中选非编码和潜在有害的编码SNV.
- 评估SNVs对SOCS3蛋白质稳定性,活性和基因表达的功能影响.
- 建立一个计算管道来评估瘤抑制基因中的SNVs.
主要方法:
- 使用多种生物信息学工具 (PredictSNP1.0,ConSurf,ModPred,I-Mutant,MUpro,UTRSite,SNP2TFBS,miRNA SNP) 来进行SNV分析.
- 进行了分子对接和分子动力学 (MD) 模拟,以评估SNV对SOCS3-JAK相互作用的影响.
- 对2786个SOCS3SNV进行了选,以确定编码和非编码区域中的功能性显著变异.
主要成果:
- 确定了10个编码SNP和49个影响基因功能的非编码SNP.
- 三种编码SNV (W48R,R71C,N198S) 被多种工具预测为高度破坏性.
- 一个编码SNV (R194W) 在用分子对接和MD模拟进行分析时显示出显著的有害影响.
结论:
- 该研究成功地选和识别了SOCS3基因中的功能相关SNV.
- 建议特定的SNVs (W48R,R71C,N198S,R194W) 作为SOCS3瘤抑制作用的潜在关键.
- 开发了一种全面的计算方法,用于对SNVs影响蛋白质功能和癌症风险的未来研究.
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