Abstract：
The Harvey rat sarcoma (HRAS) proto-oncogene belongs to the RAS family and is one of the pathogenic genes that cause cancer. Deleterious nsSNPs might have adverse consequences at the protein level. This study aimed to investigate deleterious nsSNPs in the HRAS gene in predicting structural alterations associated with mutants that disrupt normal protein-protein interactions. Functional and structural analysis was employed in analyzing the HRAS nsSNPs. Putative post-translational modification sites and the changes in protein-protein interactions, which included a variety of signal cascades, were also investigated. Five different bioinformatics tools predicted 33 nsSNPs as \"pathogenic\" or \"harmful\". Stability analysis predicted rs1554885139, rs770492627, rs1589792804, rs730880460, rs104894227, rs104894227, and rs121917759 as unstable. Protein-protein interaction analysis revealed that HRAS has a hub connecting three clusters consisting of 11 proteins, and changes in HRAS might cause signal cascades to dissociate. Furthermore, Kaplan-Meier bioinformatics analyses indicated that the HRAS gene deregulation affected the overall survival rate of patients with breast cancer, leading to prognostic significance. Thus, based on these analyses, our study suggests that the reported nsSNPs of HRAS may serve as potential targets for different proteomic studies, diagnoses, and therapeutic interventions focusing on cancer.
摘要：
哈维大鼠肉瘤(HRAS)原癌基因属于RAS家族,是引起癌症的致病基因之一。有害的nsSNP可能在蛋白质水平上具有不利后果。这项研究旨在研究HRAS基因中有害的nsSNP，以预测与破坏正常蛋白质-蛋白质相互作用的突变体相关的结构改变。功能和结构分析用于分析HRASnsSNP。推定的翻译后修饰位点和蛋白质-蛋白质相互作用的变化，其中包括各种信号级联，也被调查了。五种不同的生物信息学工具预测33个nsSNP为“致病性”或“有害”。稳定性分析预测rs1554885139、rs770492627、rs1589792804、rs730880460、rs104894227、rs104894227和rs121917759为不稳定。蛋白质相互作用分析表明，HRAS具有连接由11种蛋白质组成的三个簇的枢纽，HRAS的变化可能导致信号级联分离。此外，Kaplan-Meier生物信息学分析表明,HRAS基因失调影响乳腺癌患者的总体生存率,导致预后意义。因此，基于这些分析，我们的研究表明，已报道的HRAS的nsSNPs可能作为不同蛋白质组学研究的潜在目标，诊断,以及针对癌症的治疗干预措施。
