Identification of Deregulated miRNAs and mRNAs Involved in Tumorigenesis and Detection of Glioblastoma Patients Applying Next-Generation RNA Sequencing

(1) <b>Background:</b> Glioblastoma (GBM) is one of the most aggressive brain tumors with a poor prognosis. Therefore, new insights into GBM diagnosis and treatment are required. In addition to differentially expressed mRNAs, miRNAs may have the potential to be applied as diagnostic biom...

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Main Authors: Dóra Géczi, Álmos Klekner, István Balogh, András Penyige, Melinda Szilágyi, József Virga, Andrea Bakó, Bálint Nagy, Bernadett Torner, Zsuzsanna Birkó
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Language:English
Published: MDPI AG 2025-03-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/3/431
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author Dóra Géczi
Álmos Klekner
István Balogh
András Penyige
Melinda Szilágyi
József Virga
Andrea Bakó
Bálint Nagy
Bernadett Torner
Zsuzsanna Birkó
author_facet Dóra Géczi
Álmos Klekner
István Balogh
András Penyige
Melinda Szilágyi
József Virga
Andrea Bakó
Bálint Nagy
Bernadett Torner
Zsuzsanna Birkó
author_sort Dóra Géczi
collection DOAJ
description (1) <b>Background:</b> Glioblastoma (GBM) is one of the most aggressive brain tumors with a poor prognosis. Therefore, new insights into GBM diagnosis and treatment are required. In addition to differentially expressed mRNAs, miRNAs may have the potential to be applied as diagnostic biomarkers. (2) <b>Methods:</b> In this study, profiling of human miRNAs in combination with mRNAs was performed on total RNA isolated from tissue samples of five control and five GBM patients, using a high-throughput RNA sequencing (RNA-Seq) approach. (3) <b>Results:</b> A total of 35 miRNAs and 365 mRNAs were upregulated, while 82 miRNAs and 1225 mRNAs showed significant downregulation between tissue samples of GBM patients compared to the control samples using the iDEP <i>tool</i> to analyze RNA-Seq data. To validate our results, the expression of five miRNAs (hsa-miR-196a-5p, hsa-miR-21-3p, hsa-miR-10b-3p, hsa-miR-383-5p, and hsa-miR-490-3p) and fourteen mRNAs (E2F2, HOXD13, VEGFA, CDC45, AURKB, HOXC10, MYBL2, FABP6, PRLHR, NEUROD6, CBLN1, HRH3, HCN1, and RELN) was determined by RT-qPCR assay. The miRNet tool was used to build miRNA–target interaction. Furthermore, a protein–protein interaction (PPI) network was created from the miRNA targets by applying the NetworkAnalyst 3.0 tool. Based on the PPI network, a functional enrichment analysis of the target proteins was also carried out. (4) <b>Conclusions:</b> We identified an miRNA panel and several deregulated mRNAs that could play an important role in tumor development and distinguish GBM patients from healthy controls with high sensitivity and specificity using total RNA isolated from tissue samples.
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spelling doaj-art-d1328e07fba7424fa1bd804ab7dda7a92025-08-20T03:43:29ZengMDPI AGPharmaceuticals1424-82472025-03-0118343110.3390/ph18030431Identification of Deregulated miRNAs and mRNAs Involved in Tumorigenesis and Detection of Glioblastoma Patients Applying Next-Generation RNA SequencingDóra Géczi0Álmos Klekner1István Balogh2András Penyige3Melinda Szilágyi4József Virga5Andrea Bakó6Bálint Nagy7Bernadett Torner8Zsuzsanna Birkó9Department of Human Genetics, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Neurosurgery, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Human Genetics, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Human Genetics, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Human Genetics, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Oncology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Oncology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Human Genetics, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Human Genetics, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Human Genetics, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary(1) <b>Background:</b> Glioblastoma (GBM) is one of the most aggressive brain tumors with a poor prognosis. Therefore, new insights into GBM diagnosis and treatment are required. In addition to differentially expressed mRNAs, miRNAs may have the potential to be applied as diagnostic biomarkers. (2) <b>Methods:</b> In this study, profiling of human miRNAs in combination with mRNAs was performed on total RNA isolated from tissue samples of five control and five GBM patients, using a high-throughput RNA sequencing (RNA-Seq) approach. (3) <b>Results:</b> A total of 35 miRNAs and 365 mRNAs were upregulated, while 82 miRNAs and 1225 mRNAs showed significant downregulation between tissue samples of GBM patients compared to the control samples using the iDEP <i>tool</i> to analyze RNA-Seq data. To validate our results, the expression of five miRNAs (hsa-miR-196a-5p, hsa-miR-21-3p, hsa-miR-10b-3p, hsa-miR-383-5p, and hsa-miR-490-3p) and fourteen mRNAs (E2F2, HOXD13, VEGFA, CDC45, AURKB, HOXC10, MYBL2, FABP6, PRLHR, NEUROD6, CBLN1, HRH3, HCN1, and RELN) was determined by RT-qPCR assay. The miRNet tool was used to build miRNA–target interaction. Furthermore, a protein–protein interaction (PPI) network was created from the miRNA targets by applying the NetworkAnalyst 3.0 tool. Based on the PPI network, a functional enrichment analysis of the target proteins was also carried out. (4) <b>Conclusions:</b> We identified an miRNA panel and several deregulated mRNAs that could play an important role in tumor development and distinguish GBM patients from healthy controls with high sensitivity and specificity using total RNA isolated from tissue samples.https://www.mdpi.com/1424-8247/18/3/431glioblastomamiRNAsbrain tissuenext-generation sequencingbiomarker
spellingShingle Dóra Géczi
Álmos Klekner
István Balogh
András Penyige
Melinda Szilágyi
József Virga
Andrea Bakó
Bálint Nagy
Bernadett Torner
Zsuzsanna Birkó
Identification of Deregulated miRNAs and mRNAs Involved in Tumorigenesis and Detection of Glioblastoma Patients Applying Next-Generation RNA Sequencing
Pharmaceuticals
glioblastoma
miRNAs
brain tissue
next-generation sequencing
biomarker
title Identification of Deregulated miRNAs and mRNAs Involved in Tumorigenesis and Detection of Glioblastoma Patients Applying Next-Generation RNA Sequencing
title_full Identification of Deregulated miRNAs and mRNAs Involved in Tumorigenesis and Detection of Glioblastoma Patients Applying Next-Generation RNA Sequencing
title_fullStr Identification of Deregulated miRNAs and mRNAs Involved in Tumorigenesis and Detection of Glioblastoma Patients Applying Next-Generation RNA Sequencing
title_full_unstemmed Identification of Deregulated miRNAs and mRNAs Involved in Tumorigenesis and Detection of Glioblastoma Patients Applying Next-Generation RNA Sequencing
title_short Identification of Deregulated miRNAs and mRNAs Involved in Tumorigenesis and Detection of Glioblastoma Patients Applying Next-Generation RNA Sequencing
title_sort identification of deregulated mirnas and mrnas involved in tumorigenesis and detection of glioblastoma patients applying next generation rna sequencing
topic glioblastoma
miRNAs
brain tissue
next-generation sequencing
biomarker
url https://www.mdpi.com/1424-8247/18/3/431
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