Identification of Deregulated miRNAs and mRNAs Involved in Tumorigenesis and Detection of Glioblastoma Patients Applying Next-Generation RNA Sequencing
Abstract
:1. Introduction
2. Results
2.1. Identification of Differently Expressed (DE) miRNAs in Tissue Samples of GBM Patients and Control Group
2.1.1. Next-Generation Sequencing (NGS)
2.1.2. Hierarchical Clustering with Heatmap and Principal Component (PCA) Analysis
2.1.3. Differentially Expressed Genes (DEGs)
2.1.4. miRNA Ranking by Network-Based Analysis
2.1.5. Gene Ontology (GO) and Pathway Enrichment Analysis of miRNA Targets
2.1.6. Validation of Differentially Expressed (DE) miRNAs by RT-qPCR in Tissue Samples
2.2. Identification of Differently Expressed (DE) mRNAs in Tissue Samples of GBM Patients and Control Group
2.2.1. Next-Generation Sequencing (NGS)
2.2.2. Hierarchical Clustering with Heatmap and Principal Component (PCA) Analysis
2.2.3. Differentially Expressed Genes (DEGs)
2.2.4. Protein–Protein Interaction (PPI) Network Analysis of Deregulated mRNAs
2.2.5. Gene Ontology (GO) and Pathway Enrichment Analysis of mRNA Molecules
2.2.6. Validation of Differentially Expressed (DE) mRNAs by RT-qPCR in Tissue Samples
2.3. The Correlation Between miRNA and mRNA Expression Determined by Next-Generation Sequencing (NGS)
3. Discussion
3.1. Identification of Differently Expressed (DE) miRNAs and mRNAs in Tissue Samples of GBM Patients in Combination with Pathway and Gene Ontology (GO) Enrichment Analysis
3.2. Validation of Differentially Expressed (DE) miRNAs by RT-qPCR in Tissue Samples
3.3. Validation of Differentially Expressed (DE) mRNAs by RT-qPCR in Tissue Samples
3.4. The Correlation Between miRNA and mRNA Expression Determined by Next-Generation Sequencing (NGS)
4. Materials and Methods
4.1. Patients and Samples
4.2. Tissue Exploration and RNA Isolation and Purification for Next-Generation Sequencing (NGS)
4.3. Next-Generation Sequencing (NGS) and Determination of Differentially Expressed (DE) miRNAs and mRNAs
4.4. Prediction of Targets of Differentially Expressed (DE) miRNAs, Construction of PPI Networks, Gene Ontology (GO), and Functional Annotation and Pathway Enrichment Analysis
4.5. Validation of miRNA-Seq Results by Quantitative Real-Time PCR (RT-qPCR)
4.6. Validation of mRNA-Seq Results by Quantitative Real-Time PCR (RT-qPCR)
4.7. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Regulated Gene | Biological Process | Expression Status (Up/Down) | miRNA | Expression Status (Up/Down) | References |
---|---|---|---|---|---|
AHR | regulation of transcription | up | hsa-mir-124-3p | down | [19] |
E2F2 | regulation of transcription | up | hsa-mir-218-5p | down | [20] |
HOXC10 | regulation of transcription | up | hsa-mir-129-5p | down | [21] |
HOXD4 | regulation of transcription | up | hsa-mir-10b | up | [22,23] |
MYBL2 | regulation of transcription | up | hsa-mir-30e-5p | down | [24] |
NEUROD2 | regulation of transcription | down | hsa-mir-210-3p | up | [25] |
AJAP1 | cell adhesion | down | hsa-mir-196a-5p | up | [26] |
MMP9 | cell migration | up | hsa-mir-490-3p | down | [27] |
POSTN | cell migration | up | hsa-mir-340-5p | down | [28] |
STC2 | cell migration | up | hsa-mir-381-3p | down | [29] |
GABRA1 | synaptic transmission | down | hsa-mir-155 -5p | up | [30] |
GABRB2 | synaptic transmission | down | hsa-mir-10a-5p hsa-mir-10b-5p | up | [31,32] |
HCN1 | transmission of nerve impulse | down | hsa-mir-10a-5p hsa-mir-10b-5p | up | [33] |
AURKA | cell cycle regulation | up | hsa-mir-124-3p | down | [34] |
AURKB | cell cycle regulation | up | hsa-miR-93-5p, hsa-miR-17-5p, hsa-miR-130b-3p | up | [34] |
CDC45 | cell cycle regulation | up | hsa-mir-485-5p | down | [35] |
CDK6 | cell cycle regulation | up | hsa-mir-107 | down | [36] |
EGFR | cell proliferation | up | hsa-mir-7 | down | [37] |
VEGFA | cell proliferation angiogenesis | up | hsa-mir-383-5p | down | [38] |
LTBP-1 | regulation of tumor-associated macrophages | up | hsa-mir-340-5p | down | [28] |
POSTN | regulation of tumor-associated macrophages | up | hsa-mir-340-5p | down | [28] |
BCL2 | apoptosis | up | hsa-mir-136-3p | down | [39] |
EZH2 | epigenetic regulation | up | hsa-miR-138-5p, hsa-miR-490-3p | down | [40,41] |
(a) | |||
Members of NGS | Gender | Age | Immunohistochemical characteristics |
Control_1 | M | 70 | - |
Control_2 | M | 52 | - |
Control_3 | M | 52 | - |
Control_4 | F | 71 | - |
Control_5 | F | 80 | - |
GBM_1 | M | 65 | IDH wild type |
GBM_2 | M | 57 | IDH wild type |
GBM_3 | M | 70 | IDH wild type- |
GBM_4 | F | 60 | IDH wild type- |
GBM_5 | F | 56 | IDH wild type- |
(b) | |||
Characteristic | Control Group (number) | GBM Group (number) | |
Sex (M/F) | 14/14 | 15/15 | |
Age | |||
Median | 63 | 61 | |
Range | 38–78 | 37–80 |
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Géczi, D.; Klekner, Á.; Balogh, I.; Penyige, A.; Szilágyi, M.; Virga, J.; Bakó, A.; Nagy, B.; Torner, B.; Birkó, Z. Identification of Deregulated miRNAs and mRNAs Involved in Tumorigenesis and Detection of Glioblastoma Patients Applying Next-Generation RNA Sequencing. Pharmaceuticals 2025, 18, 431. https://doi.org/10.3390/ph18030431
Géczi D, Klekner Á, Balogh I, Penyige A, Szilágyi M, Virga J, Bakó A, Nagy B, Torner B, Birkó Z. Identification of Deregulated miRNAs and mRNAs Involved in Tumorigenesis and Detection of Glioblastoma Patients Applying Next-Generation RNA Sequencing. Pharmaceuticals. 2025; 18(3):431. https://doi.org/10.3390/ph18030431
Chicago/Turabian StyleGéczi, Dóra, Álmos Klekner, István Balogh, András Penyige, Melinda Szilágyi, József Virga, Andrea Bakó, Bálint Nagy, Bernadett Torner, and Zsuzsanna Birkó. 2025. "Identification of Deregulated miRNAs and mRNAs Involved in Tumorigenesis and Detection of Glioblastoma Patients Applying Next-Generation RNA Sequencing" Pharmaceuticals 18, no. 3: 431. https://doi.org/10.3390/ph18030431
APA StyleGéczi, D., Klekner, Á., Balogh, I., Penyige, A., Szilágyi, M., Virga, J., Bakó, A., Nagy, B., Torner, B., & Birkó, Z. (2025). Identification of Deregulated miRNAs and mRNAs Involved in Tumorigenesis and Detection of Glioblastoma Patients Applying Next-Generation RNA Sequencing. Pharmaceuticals, 18(3), 431. https://doi.org/10.3390/ph18030431