Molecular pathways in glioblastoma-derived stem cells to identify effective drug agents: A bioinformatics study
Tahereh Mirzaei1, Seyed Amir Sheikholeslami2, Ahmad Bereimipour3,4
1Nargund College of Pharmacy, Rajiv Gandhi University of Health Sciences, Bengaluru, Karnataka, India.
Background And Aim:
Glioblastoma multiform (GBM) is considered as one of the malignant brain tumors that affect a wide range of people every year. Cancer stem cells, as essential factors, are resistant to chemotherapy drugs and complicate treatments. Therefore, finding critical molecular pathways in GBM-derived stem cells, and selecting the appropriate drug agents can prove more effective treatment approaches for GBM.
Method:
In this study, using RNA-Seq data, we performed continuous bioinformatics analyses and examined the up-and down-regulated genes from GBM-derived stem cells samples. Afterward, we separated the signaling pathways using the KEGG database and measured the protein interactions with the STRING database. Then, using the Drug matrix database, we nominated drugs that could affect these genes.
Results:
The first 20 pathways on tumorigenesis and 41 up-regulated and 73 down-regulated genes were selected. These genes were most active in the pathways involved in cell division, metabolism, cytoskeleton, cell adhesion molecules, and extracellular space. We then examined the candidate genes and the approach of the drugs that target these genes. Chlorambucil, cyclosporine A, doxorubicin, and etoposide were selected as the drug agents.
Conclusion:
Using integrated bioinformatics analyses, it was found that prominent genes in the cell cycle and cytoskeletal pathways are more expressed in cancer stem cells and that Chlorambucil, cyclosporine A, doxorubicin, and etoposide can be effective compounds to attenuate these cells.
Insights
This study identifies key cell cycle and cytoskeletal genes in glioblastoma (GBM) stem cells. Chlorambucil, cyclosporine A, doxorubicin, and etoposide show potential for treating these resistant GBM cells.
Area of Science:
- Oncology
- Bioinformatics
- Genomics
Background:
- Glioblastoma multiform (GBM) is a deadly brain tumor.
- GBM stem cells resist chemotherapy, complicating treatment.
- Identifying molecular targets in GBM stem cells is crucial for effective therapies.
Purpose of the Study:
- To identify differentially expressed genes and critical molecular pathways in GBM-derived stem cells.
- To nominate potential drug agents targeting these pathways for GBM treatment.
Main Methods:
- RNA-sequencing data analysis of GBM stem cells.
- Pathway analysis using KEGG database.
- Protein-protein interaction analysis using STRING database.
- Drug target identification using Drug matrix database.
Main Results:
- Identified 20 key tumorigenesis pathways.
- Found 41 up-regulated and 73 down-regulated genes.
- Selected genes are involved in cell division, metabolism, cytoskeleton, and cell adhesion.
- Chlorambucil, cyclosporine A, doxorubicin, and etoposide were nominated as potential drugs.
Conclusions:
- Genes in cell cycle and cytoskeletal pathways are highly expressed in GBM stem cells.
- Chlorambucil, cyclosporine A, doxorubicin, and etoposide may effectively target and attenuate GBM stem cells.
