Wanarase Shubham Ramdas, Chavan Shivam Vinayakrao, Sharma Sameer, D Susha
Department of Bioinformatics, BioNome, Bengaluru, Karnataka, India.
J Biomol Struct Dyn. 2023;41(23):13937-13949. doi: 10.1080/07391102.2023.2192793. Epub 2023 Mar 22.
In the bloodstream and in local tissues, most IGF molecules are associated with the one of the members of the IGF-binding protein (IGFBP) family, which are divided into six distinct types. IGF-binding proteins have been demonstrated to either decrease or increase the growth-promoting effects of IGFs on cell culture, by extending their half-life. They alter how IGFs interact with the receptors on their cell surfaces. gene is associated with disease carcinoma. Upregulation or downregulation of gene has been implicated in different types of cancer in humans. Nonsynonymous SNPs changes have the potential to affect the protein's structure and function. Potential functional SNPs can be assessed before undertaking studies in larger populations because validation of these functional SNPs can be a crucial problem. So, in this investigation, we used a variety of sequence- and structure-based bioinformatics methods to separate the potential nsSNPs of the gene from the neutral ones. In total of 216 nsSNPs, 5 were found to have potential effects using 5 prediction tools. From which, 2 nsSNPs (R128G and R164H) were selected as potentially damaging due to their presence in highly conserved region and ability to decrease protein stability. Among these 2 nsSNPs, only R164H was found to be associated with Uterine corpus endometrial carcinoma. It was also found that both, upregulation or downregulation of gene can lead to the different types of cancers. The findings of the present study will certainly be valuable in the future large population-based investigations as well as drug discovery, especially developing personalized medicine.Communicated by Ramaswamy H. Sarma.
在血液和局部组织中，大多数胰岛素样生长因子（IGF）分子与IGF结合蛋白（IGFBP）家族的成员之一相关联，该家族分为六种不同类型。已证明IGF结合蛋白通过延长其半衰期来降低或增强IGF对细胞培养的促生长作用。它们改变了IGF与细胞表面受体的相互作用方式。 基因与疾病 癌相关。该基因的上调或下调与人类不同类型的癌症有关。非同义单核苷酸多态性（SNP）变化有可能影响蛋白质的结构和功能。在对更大规模人群进行研究之前，可以评估潜在的功能性SNP，因为验证这些功能性SNP可能是一个关键问题。因此，在本研究中，我们使用了多种基于序列和结构的生物信息学方法，将该基因的潜在非同义SNP与中性SNP区分开来。在总共216个非同义SNP中，使用5种预测工具发现有5个具有潜在影响。其中，2个非同义SNP（R128G和R164H）由于存在于高度保守区域且能够降低蛋白质稳定性而被选为具有潜在损害性。在这2个非同义SNP中，仅发现R164H与子宫内膜癌相关。还发现该基因的上调或下调均可导致不同类型的癌症。本研究的结果在未来基于大规模人群的调查以及药物发现，特别是开发个性化药物方面肯定具有价值。由拉马斯瓦米·H·萨尔马传达。
