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Integrated Bioinformatics Analysis of Differentially Expressed RNA-Binding Proteins in Human Gliomas
Shafiul Haque1,2, Darin Mansor Mathkor1, Ashjan Saeed Babegi1
1Department of Nursing, College of Nursing and Health Sciences, Jazan University, Jazan, 82911, Saudi Arabia.
Abstract:
Gliomas are complex and among the most lethal central nervous system (CNS) disorders. While they are notoriously heterogeneous, evidences suggest critical involvement of intricate interactions between RNA-binding proteins (RBPs) and their diverse partners, in the pathogeneses of gliomas. In this study, we used RNA sequencing data from the Cancer Genome Atlas (TCGA) to identify differentially expressed genes (DEGs). After selection of differentially expressed RBPs from these DEGs, systematic investigation of their transcriptomic changes during glioma progression was undertaken. Extensive in silico assessments allowed the creation of their interactome and pathway, identifying potential biological effects of these differentially expressed RBPs. Construction of regulatory networks of these differentially expressed RBPs and their topological analysis discovered key RBPs such as PABPC1, EIF4A2, RPS3, EEF1A1, RPS6, ELAVL2, CPEB1, and CELF5, which are largely involved in alternative splicing and ribosomal biogenesis. Moreover, we also identified differentially expressed RBPs such as YBX1, ELAVL2, and IGF2BP1, which may be involved in the formation of stress granules in gliomas. We also identified highly mutated RBPs, such as RPSA, RPL5, CPEB4, and SMAD7, in gliomas. Further, RBPs like RPS8, RPL5, RPS3A, EEF1A1, and EIF4E1B were found to be strongly correlated with patients' overall survival. Taken together, our analyses identified several candidate RBPs which might serve as potential targets for oncological measures against gliomas.
Insights
This study identifies key RNA-binding proteins (RBPs) involved in glioma development and progression. These RBPs, implicated in splicing and ribosome biogenesis, represent potential therapeutic targets for brain tumors.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Genomics
Background:
- Gliomas are lethal central nervous system (CNS) cancers characterized by significant heterogeneity.
- Interactions involving RNA-binding proteins (RBPs) are increasingly recognized as critical in glioma pathogenesis.
Purpose of the Study:
- To identify and characterize differentially expressed RBPs in gliomas.
- To explore the functional roles and regulatory networks of these RBPs in glioma progression.
- To discover potential therapeutic targets among dysregulated RBPs.
Main Methods:
- Utilized RNA sequencing data from The Cancer Genome Atlas (TCGA) to identify differentially expressed genes (DEGs).
- Selected differentially expressed RBPs and analyzed their transcriptomic changes, interactome, and pathways using in silico methods.
- Constructed and topologically analyzed regulatory networks of identified RBPs.
Main Results:
- Identified key RBPs (e.g., PABPC1, EIF4A2, RPS3) involved in alternative splicing and ribosomal biogenesis.
- Found RBPs (e.g., YBX1, ELAVL2) potentially associated with stress granule formation in gliomas.
- Highlighted mutated RBPs (e.g., RPSA, RPL5) and RBPs (e.g., RPS8, EEF1A1) correlated with patient survival.
Conclusions:
- Several candidate RBPs show significant alterations and correlations with glioma progression and patient outcomes.
- These identified RBPs, particularly those in splicing and ribosome biogenesis, are promising targets for novel glioma therapies.
- Further investigation into these RBPs could lead to advancements in oncological strategies against gliomas.
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