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Updated: Jun 6, 2026
Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
Identification of hub mRNAs and long non-coding RNAs involved in temozolomide-resistant glioblastoma (brain cancer)
Mostafa Alamholo1,2, Alireza Tarinejad3
1Department of Biotechnology and Biomedicine, Institute of Science and Modern Technology, Rojava University, Qamishlo, Syria. mostafaalamholo@yahoo.com.
Purpose:
Temozolomide (TMZ) is used to treat glioblastoma cancer and it is essential to identify key genes and investigate the molecular mechanisms of glioblastoma cancer cells resistant to temozolomide.
Materials And Methods:
Raw RNA-Seq data from glioblastoma cell lines were analyzed by Linux and used to align to the human reference genome GRCh38 using HISAT2 as well as edgeR in the R package was used. KEGG and EnrichR pathways were used for enrichment analysis and degree level in Cytoscape was used to identify hub genes.
Results:
The top up-regulated genes included NeuroD4, IgSF21, PCDH8, ACKR1, and TC2N, and top down-regulated genes including ITGAX, SIGLEC-15, CCL8, MOG, PENK, and SELE were identified. The genes up-expressed in the biological process (BP) were mostly related to regulation of phospholipase c-activating G protein-coupled receptor signaling pathway, in the molecular function (MF) belonged to calcium- dependent cysteine-type endopeptidase activity, and in the cellular component (CC) were associated with actin filament. Next, the genes down-expressed in the BP were mainly related to cytokine-mediated signaling pathway, in the MF related to chemokine receptor binding, and in the CC were belonged to MHC Class II protein complex. Key genes related to KEGG pathways mainly were shown chemokine, inflammations, apoptosis, and cell adhesion functions. Top up-regulated TFs including TFAP2C, and BCL11A and top down-regulated TFs such as IRF3, and CEBPB were identified. Top up-regulated hub genes including NEUROD1, DCX, and ACKR1 and top down-regulated hub genes such as IL1B, CXCL10, and ITGAX were identified. Top up-regulated lncRNAs including NAV2-AS2, CAMTA1-AS2, and MEIS1-AS3, and top down-regulated lncRNAs such as MIR3142HG, SUGCT-AS1, and DBH-AS1 were identified. Finally, this study was evaluated with qRT-PCR results of reported studies and the expression of down and up-regulated genes was confirmed.
Conclusion:
Accordingly, these genes can be incorporated into clinical prognostic models and provide panels of genes for selecting personalized and appropriate therapeutic approaches. Overall, key genes can be suggested as influential genes associated with temozolomide-resistant glioblastoma cell lines.
Insights
This study identifies key genes and molecular mechanisms in temozolomide-resistant glioblastoma. These findings can inform personalized treatment strategies for glioblastoma cancer.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Glioblastoma is a primary brain tumor with poor prognosis.
- Temozolomide (TMZ) is a standard chemotherapy, but resistance is a major challenge.
- Understanding molecular mechanisms of TMZ resistance is crucial for improving treatment outcomes.
Purpose of the Study:
- To identify key genes and molecular mechanisms underlying temozolomide resistance in glioblastoma.
- To investigate gene expression profiles in temozolomide-resistant glioblastoma cell lines.
Main Methods:
- Analysis of raw RNA-Seq data from glioblastoma cell lines.
- Alignment to the human reference genome GRCh38 using HISAT2.
- Differential gene expression analysis using edgeR.
- Pathway enrichment analysis using KEGG and EnrichR.
- Identification of hub genes and transcription factors using Cytoscape.
Main Results:
- Identified top up-regulated genes (e.g., NeuroD4, IgSF21) and down-regulated genes (e.g., ITGAX, CCL8).
- Up-regulated genes were associated with G-protein coupled receptor signaling, while down-regulated genes were linked to cytokine-mediated signaling and chemokine receptor binding.
- Key genes involved in chemokine, inflammation, apoptosis, and cell adhesion pathways were identified.
- Identified significant transcription factors, hub genes, and long non-coding RNAs (lncRNAs) associated with TMZ resistance.
Conclusions:
- The identified genes can be integrated into clinical prognostic models for glioblastoma.
- Gene panels can aid in selecting personalized therapeutic approaches for TMZ-resistant glioblastoma.
- These key genes represent potential therapeutic targets for overcoming temozolomide resistance.
