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In silico analysis identified miRNA-based therapeutic agents against glioblastoma multiforme

MicroRNAs (miRNAs or miRs) contribute to the development of various malignant neoplasms, including glioblastoma multiforme (GBM). The present study aimed to explore the pathogenesis of GBM and to identify latent therapeutic agents for patients with GBM, based on an in silico analysis. Gene chips tha...

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Autores principales: Xiong, Dan-Dan, Xu, Wen-Qing, He, Rong-Quan, Dang, Yi-Wu, Chen, Gang, Luo, Dian-Zhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412522/
https://www.ncbi.nlm.nih.gov/pubmed/30816530
http://dx.doi.org/10.3892/or.2019.7022
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author Xiong, Dan-Dan
Xu, Wen-Qing
He, Rong-Quan
Dang, Yi-Wu
Chen, Gang
Luo, Dian-Zhong
author_facet Xiong, Dan-Dan
Xu, Wen-Qing
He, Rong-Quan
Dang, Yi-Wu
Chen, Gang
Luo, Dian-Zhong
author_sort Xiong, Dan-Dan
collection PubMed
description MicroRNAs (miRNAs or miRs) contribute to the development of various malignant neoplasms, including glioblastoma multiforme (GBM). The present study aimed to explore the pathogenesis of GBM and to identify latent therapeutic agents for patients with GBM, based on an in silico analysis. Gene chips that provide miRNA expression profiling in GBM were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DEMs) were also determined via the RobustRankAggreg algorithm. The target genes of DEMs were predicted and then intersected with GBM-associated genes that were collected from the Gene Expression Profiling Interactive Analysis. Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the overlapping genes were then performed. Simultaneously, a connectivity map (CMap) analysis was performed to screen for potential therapeutic agents for GBM. A total of 10 DEMs (hsa-miR-196a, hsa-miR-10b, hsa-miR-196b, hsa-miR-18b, hsa-miR-542-3p, hsa-miR-129-3p, hsa-miR-1224-5p, hsa-miR-876-3p and hsa-miR-770-5p) were obtained from three GEO gene chips (GSE25631, GSE42657 and GSE61710). Then, 1,720 target genes of the 10 miRNAs and 4,185 differently expressed genes in GBM were collected. By intersecting the aforementioned gene clusters, the present study identified 390 overlapping genes. GO and KEGG analyses of the 390 genes demonstrated that these genes were involved in certain cancer-associated biological functions and pathways. Eight genes [(GTPase NRas (NRAS), calcium/calmodulin-dependent protein kinase type II subunit Gamma (CAMK2G), platelet-derived growth factor receptor alpha (PDGFRA), calmodulin 3 (CALM3), cyclin-dependent kinase 6 (CDK6), calcium/calmodulin-dependent protein kinase type II subunit beta (CAMK2B), retinoblastoma-associated protein (RB1) and protein kinase C beta type (PRKCB)] that were centralized in the glioma pathway were selected for CMap analysis. Three chemicals (W-13, gefitinib and exemestane) were identified as putative therapeutic agents for GBM. In summary, the present study identified three miRNA-based chemicals for use as a therapy for GBM. However, more experimental data are needed to verify the therapeutic properties of these latent drugs in GBM.
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spelling pubmed-64125222019-03-19 In silico analysis identified miRNA-based therapeutic agents against glioblastoma multiforme Xiong, Dan-Dan Xu, Wen-Qing He, Rong-Quan Dang, Yi-Wu Chen, Gang Luo, Dian-Zhong Oncol Rep Articles MicroRNAs (miRNAs or miRs) contribute to the development of various malignant neoplasms, including glioblastoma multiforme (GBM). The present study aimed to explore the pathogenesis of GBM and to identify latent therapeutic agents for patients with GBM, based on an in silico analysis. Gene chips that provide miRNA expression profiling in GBM were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DEMs) were also determined via the RobustRankAggreg algorithm. The target genes of DEMs were predicted and then intersected with GBM-associated genes that were collected from the Gene Expression Profiling Interactive Analysis. Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the overlapping genes were then performed. Simultaneously, a connectivity map (CMap) analysis was performed to screen for potential therapeutic agents for GBM. A total of 10 DEMs (hsa-miR-196a, hsa-miR-10b, hsa-miR-196b, hsa-miR-18b, hsa-miR-542-3p, hsa-miR-129-3p, hsa-miR-1224-5p, hsa-miR-876-3p and hsa-miR-770-5p) were obtained from three GEO gene chips (GSE25631, GSE42657 and GSE61710). Then, 1,720 target genes of the 10 miRNAs and 4,185 differently expressed genes in GBM were collected. By intersecting the aforementioned gene clusters, the present study identified 390 overlapping genes. GO and KEGG analyses of the 390 genes demonstrated that these genes were involved in certain cancer-associated biological functions and pathways. Eight genes [(GTPase NRas (NRAS), calcium/calmodulin-dependent protein kinase type II subunit Gamma (CAMK2G), platelet-derived growth factor receptor alpha (PDGFRA), calmodulin 3 (CALM3), cyclin-dependent kinase 6 (CDK6), calcium/calmodulin-dependent protein kinase type II subunit beta (CAMK2B), retinoblastoma-associated protein (RB1) and protein kinase C beta type (PRKCB)] that were centralized in the glioma pathway were selected for CMap analysis. Three chemicals (W-13, gefitinib and exemestane) were identified as putative therapeutic agents for GBM. In summary, the present study identified three miRNA-based chemicals for use as a therapy for GBM. However, more experimental data are needed to verify the therapeutic properties of these latent drugs in GBM. D.A. Spandidos 2019-04 2019-02-19 /pmc/articles/PMC6412522/ /pubmed/30816530 http://dx.doi.org/10.3892/or.2019.7022 Text en Copyright: © Xiong et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Xiong, Dan-Dan
Xu, Wen-Qing
He, Rong-Quan
Dang, Yi-Wu
Chen, Gang
Luo, Dian-Zhong
In silico analysis identified miRNA-based therapeutic agents against glioblastoma multiforme
title In silico analysis identified miRNA-based therapeutic agents against glioblastoma multiforme
title_full In silico analysis identified miRNA-based therapeutic agents against glioblastoma multiforme
title_fullStr In silico analysis identified miRNA-based therapeutic agents against glioblastoma multiforme
title_full_unstemmed In silico analysis identified miRNA-based therapeutic agents against glioblastoma multiforme
title_short In silico analysis identified miRNA-based therapeutic agents against glioblastoma multiforme
title_sort in silico analysis identified mirna-based therapeutic agents against glioblastoma multiforme
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412522/
https://www.ncbi.nlm.nih.gov/pubmed/30816530
http://dx.doi.org/10.3892/or.2019.7022
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