{"title":"通过组学分析和虚拟筛选药物预测,分析HSP90AB1和其他热休克蛋白在对抗胶质母细胞瘤和室管膜瘤中的功能意义。","authors":"Sudhanshu Sharma, Pravir Kumar","doi":"10.1016/j.npep.2023.102383","DOIUrl":null,"url":null,"abstract":"<div><p><span>Heat shock proteins (HSPs) are the evolutionary family of proteins that are highly conserved and present widely in various organisms and play an array of important roles and cellular functions. Currently, very few or no studies are based on the systematic analysis of the HSPs in </span>Glioblastoma<span><span><span> (GBMs) and ependymomas. We performed an integrated </span>omics<span> analysis to predict the mutual regulatory differential HSP signatures that were associated with both glioblastoma and ependymomas. Further, we explored the various common dysregulated biological processes<span><span><span><span> operating in both the tumors, and were analyzed using functional enrichment, gene ontology along with the pathway analysis of the predicted HSPs. We established an </span>interactome network of protein-protein interaction (PPIN) to identify the hub HSPs that were commonly associated with GBMs and ependymoma. To understand the mutual molecular mechanism of the HSPs in both </span>malignancies, transcription factors, and </span>miRNAs<span> overlapping with both diseases were explored. Moreover, a transcription factor-miRNAs-HSPs coregulatory network was constructed along with the prediction of potential candidate </span></span></span></span>drugs<span> that were based on perturbation-induced gene expression analysis. Based on the RNA-sequencing data, HSP90AB1 was identified as the most promising target among other predicted HSPs. Finally, the ranking of the drugs was arranged based on various drug scores. In conclusion, this study gave a spotlight on the mutual targetable HSPs, biological pathways, and regulatory signatures associated with GBMs and ependymoma with an improved understanding of crosstalk involved. Additionally, the role of therapeutics was also explored against HSP90AB1. These findings could potentially be able to explain the interplay of HSP90AB1 and other HSPs within these two malignancies.</span></span></p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"102 ","pages":"Article 102383"},"PeriodicalIF":2.5000,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Dissecting the functional significance of HSP90AB1 and other heat shock proteins in countering glioblastomas and ependymomas using omics analysis and drug prediction using virtual screening\",\"authors\":\"Sudhanshu Sharma, Pravir Kumar\",\"doi\":\"10.1016/j.npep.2023.102383\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span>Heat shock proteins (HSPs) are the evolutionary family of proteins that are highly conserved and present widely in various organisms and play an array of important roles and cellular functions. Currently, very few or no studies are based on the systematic analysis of the HSPs in </span>Glioblastoma<span><span><span> (GBMs) and ependymomas. We performed an integrated </span>omics<span> analysis to predict the mutual regulatory differential HSP signatures that were associated with both glioblastoma and ependymomas. Further, we explored the various common dysregulated biological processes<span><span><span><span> operating in both the tumors, and were analyzed using functional enrichment, gene ontology along with the pathway analysis of the predicted HSPs. We established an </span>interactome network of protein-protein interaction (PPIN) to identify the hub HSPs that were commonly associated with GBMs and ependymoma. To understand the mutual molecular mechanism of the HSPs in both </span>malignancies, transcription factors, and </span>miRNAs<span> overlapping with both diseases were explored. Moreover, a transcription factor-miRNAs-HSPs coregulatory network was constructed along with the prediction of potential candidate </span></span></span></span>drugs<span> that were based on perturbation-induced gene expression analysis. Based on the RNA-sequencing data, HSP90AB1 was identified as the most promising target among other predicted HSPs. Finally, the ranking of the drugs was arranged based on various drug scores. In conclusion, this study gave a spotlight on the mutual targetable HSPs, biological pathways, and regulatory signatures associated with GBMs and ependymoma with an improved understanding of crosstalk involved. Additionally, the role of therapeutics was also explored against HSP90AB1. These findings could potentially be able to explain the interplay of HSP90AB1 and other HSPs within these two malignancies.</span></span></p></div>\",\"PeriodicalId\":19254,\"journal\":{\"name\":\"Neuropeptides\",\"volume\":\"102 \",\"pages\":\"Article 102383\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2023-09-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuropeptides\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0143417923000641\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuropeptides","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0143417923000641","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Dissecting the functional significance of HSP90AB1 and other heat shock proteins in countering glioblastomas and ependymomas using omics analysis and drug prediction using virtual screening
Heat shock proteins (HSPs) are the evolutionary family of proteins that are highly conserved and present widely in various organisms and play an array of important roles and cellular functions. Currently, very few or no studies are based on the systematic analysis of the HSPs in Glioblastoma (GBMs) and ependymomas. We performed an integrated omics analysis to predict the mutual regulatory differential HSP signatures that were associated with both glioblastoma and ependymomas. Further, we explored the various common dysregulated biological processes operating in both the tumors, and were analyzed using functional enrichment, gene ontology along with the pathway analysis of the predicted HSPs. We established an interactome network of protein-protein interaction (PPIN) to identify the hub HSPs that were commonly associated with GBMs and ependymoma. To understand the mutual molecular mechanism of the HSPs in both malignancies, transcription factors, and miRNAs overlapping with both diseases were explored. Moreover, a transcription factor-miRNAs-HSPs coregulatory network was constructed along with the prediction of potential candidate drugs that were based on perturbation-induced gene expression analysis. Based on the RNA-sequencing data, HSP90AB1 was identified as the most promising target among other predicted HSPs. Finally, the ranking of the drugs was arranged based on various drug scores. In conclusion, this study gave a spotlight on the mutual targetable HSPs, biological pathways, and regulatory signatures associated with GBMs and ependymoma with an improved understanding of crosstalk involved. Additionally, the role of therapeutics was also explored against HSP90AB1. These findings could potentially be able to explain the interplay of HSP90AB1 and other HSPs within these two malignancies.
期刊介绍:
The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems.
The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.