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LSM2 drives glioma progression through alternative splicing dysregulation: a multi-omics approach to identify a
Cao Yang1, Chang Ge1, Wenjie Zhang1
1Department of Neurosurgery, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Background:
Glioma, particularly glioblastoma (GBM), remains a highly aggressive and challenging tumour, characterised by poor prognosis and limited therapeutic options. LSM2, an RNA-binding protein, has been implicated in tumour progression, yet its role in glioma remains underexplored. This study aims to investigate the expression, prognostic significance, and molecular mechanisms of LSM2 in glioma, focusing on its impact on RNA splicing regulation.
Methods:
Clinical and transcriptomic data from 163 GBM and 518 lower-grade glioma (LGG) cases from The Cancer Genome Atlas (TCGA) were analysed to assess LSM2 expression and its prognostic value. RNA sequencing was performed on LSM2 knockdown in T98G glioblastoma cells to identify differentially expressed genes (DEGs) and alternative splicing events (ASEs). Bioinformatics tools were employed to perform functional enrichment analyses and construct protein-protein interaction (PPI) networks.
Results:
LSM2 expression was significantly elevated in gliomas, particularly in GBM and in tumours with 1p/19q non-deletion or IDH1 mutation (p < 0.001). High LSM2 expression was correlated with shorter overall survival (HR = 1.7, p = 0.01). Knockdown of LSM2 in T98G cells identified 728 upregulated and 1,720 downregulated genes, alongside 1,949 splicing alterations, which primarily affected pathways related to RNA metabolism, DNA damage response, and cell cycle regulation. Key hub genes such as TLN1, FN1, and IRF7 were associated with glioma progression and poor prognosis.
Conclusion:
Our findings demonstrate that LSM2 plays a critical role in glioma progression through the regulation of RNA splicing dynamics. Elevated LSM2 expression serves as a prognostic biomarker and offers promising potential as a therapeutic target in glioma.
Insights
Elevated LSM2 expression is linked to glioma progression and poor survival. This RNA-binding protein regulates RNA splicing, offering a potential therapeutic target for aggressive brain tumors like glioblastoma.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Glioma, especially glioblastoma (GBM), is an aggressive brain tumor with poor prognosis.
- The role of LSM2, an RNA-binding protein, in glioma pathogenesis is not well understood.
- Limited therapeutic options exist for glioma patients.
Purpose of the Study:
- To investigate LSM2 expression in glioma.
- To determine the prognostic significance of LSM2 in glioma.
- To elucidate the molecular mechanisms of LSM2 in glioma, focusing on RNA splicing regulation.
Main Methods:
- Analysis of clinical and transcriptomic data from The Cancer Genome Atlas (TCGA) for GBM and lower-grade glioma (LGG) cases.
- RNA sequencing following LSM2 knockdown in T98G glioblastoma cells to identify differentially expressed genes and alternative splicing events.
- Bioinformatics analysis including functional enrichment and protein-protein interaction network construction.
Main Results:
- LSM2 expression was significantly higher in gliomas, particularly GBM, and associated with poor prognostic markers.
- High LSM2 expression correlated with shorter overall survival in glioma patients.
- LSM2 knockdown altered gene expression and splicing, impacting RNA metabolism, DNA damage response, and cell cycle pathways.
Conclusions:
- LSM2 is crucial for glioma progression via regulation of RNA splicing.
- Elevated LSM2 expression is a prognostic biomarker for glioma.
- LSM2 presents a potential therapeutic target for glioma treatment.
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