生物信息学驱动的人类原瘤基因SRC中的致病性误解nsSNPs的识别和癌症易感性
Md Shakil Ahamed1, Roksana Khanam1, K M Tanjida Islam1
1Department of Biotechnology and Genetic Engineering, Mawlana Bhashani Science and Technology University, Santosh, Tangail-1902, Bangladesh.
Journal, genetic engineering & biotechnology
|December 12, 2025
概括
在SRC原基因的遗传变异可以驱动癌症. 这项研究确定了特定的SRC突变,如W151C,Y419N和P465S,这些突变影响蛋白质功能,并可能作为癌症生物标志物.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物信息学是一种生物信息学.
背景情况:
- SRC是一种原瘤基因,对细胞生长和存活至关重要.
- SRC失调是众所周知的各种癌症的驱动因素.
- SRC基因变异,特别是nsSNP的功能影响仍然不清楚.
研究的目的:
- 在SRC基因中计算识别和分析nsSNP的功能和结构后果.
- 研究SRC突变对蛋白质稳定性,蛋白质-蛋白质相互作用和药物结合的影响.
- 探索突变SRC与癌症相关基因表达模式的关联.
主要方法:
- 在SRC中对512个误解的nsSNP进行了综合计算分析.
- 预测有害的nsSNP及其对蛋白质结构稳定性的影响.
- 模拟分子动力学以评估蛋白质稳定性和结构变化.
- 蛋白质-蛋白质对接研究,以评估SRC-FAK复合物的破坏和达沙替尼结合.
- 基因表达分析,将突变的SRC与癌症相关基因联系起来.
主要成果:
- 在512个nsSNP中,42个被预测是有害的,12个破坏蛋白质结构.
- 三个关键突变 (W151C,Y419N,P465S) 导致了显著的物理化学变化和减少了蛋白质的稳定性.
- 突变破坏了SRC-FAK结合,并降低了达沙替尼的亲和力.
- 突变的SRC与失调的癌症基因相关,特别是在多发性髓瘤和子宫癌中.
结论:
- 已识别的SRC nsSNPs具有致癌潜力,改变蛋白质功能和相互作用.
- 这些突变可以作为诊断生物标志物和个性化癌症治疗的治疗点.
- 需要进一步的人口研究来验证SRC突变在癌症进展和药物反应中的作用.
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