ArticleCell death & disease2024
Modification of BCLX pre-mRNA splicing has antitumor efficacy alone or in combination with radiotherapy in human glioblastoma cells.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 11 citations in OpenAlex.
- Review
- RNA splicing in health and disease.Molecular biomedicine · 2026Review
- Transcription Factor MAX Regulates Liver Cancer Cell Growth, Migration, Invasion, and Epithelial-Mesenchymal Transition by Promoting SF3A3 Expression.World journal of oncology · 2026Article
- TIA1 depletion enhances CLSTN1 exon 11 inclusion to facilitate Epithelial-to-Mesenchymal transition and breast cancer metastasis.Oncogene · 2026Article
- ARGLU1 in Glioma: A Novel Potential Regulator of Splicing, DNA Repair, and Therapeutic Resistance.Cells · 2026Review
- Review
- RNA splicing in cancer cell death regulation: shedding light on the molecular mechanisms and potential clinical applications.Cell death & disease · 2026Review
- Targeting the PBX1-BCL2L1 axis as a therapeutic strategy in colorectal cancer.Cell death discovery · 2026Article
- β-suppressor protein 1 (ARRB1)-△exon13 modulates the progression of glioblastoma via combination with glycolysis-related proteins.Biochemistry and biophysics reports · 2025Article
- The emerging roles of aberrant alternative splicing in glioma.Cell death discovery · 2025Review
- Targeting RNA splicing modulation: new perspectives for anticancer strategy?Journal of experimental & clinical cancer research : CR · 2025Review
- Smart Physicochemical-triggered Chitosan-based Nanogels for siRNA Delivery and Gene Therapy: A Focus on Emerging Strategies and Paradigms for Cancer Therapy.Current medicinal chemistry · 2025Review
- Recent advances in spatio-temporally controllable systems for management of glioma.Asian journal of pharmaceutical sciences · 2024Review
- Glioblastoma Tumor Microenvironment: An Important Modulator for Tumoral Progression and Therapy Resistance.Current issues in molecular biology · 2024Review
- RNA structure in alternative splicing regulation: from mechanism to therapy.Acta biochimica et biophysica Sinica · 2024Review
- SNRPD2-dependency Fuels an Oncogenic Alternative Splicing Repertoire Driving Disease Aggressiveness in Glioma.Cancer genomics & proteomicsArticle
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulation of anti-apoptotic and pro-apoptotic protein isoforms arising from aberrant splicing is a crucial hallmark of cancers and may contribute to therapeutic resistance. Thus, targeting RNA splicing to redirect isoform expression of apoptosis-related genes could lead to promising anti-cancer phenotypes. Glioblastoma (GBM) is the most common type of malignant brain tumor in adults. In this study, through RT-PCR and Western Blot analysis, we found that BCLX pre-mRNA is aberrantly spliced in GBM cells with a favored splicing of anti-apoptotic Bcl-xL. Modulation of BCLX pre-mRNA splicing using splice-switching oligonucleotides (SSOs) efficiently elevated the pro-apoptotic isoform Bcl-xS at the expense of the anti-apoptotic Bcl-xL. Induction of Bcl-xS by SSOs activated apoptosis and autophagy in GBM cells. In addition, we found that ionizing radiation could also modulate the alternative splicing of BCLX. In contrast to heavy (carbon) ion irradiation, low energy X-ray radiation-induced an increased ratio of Bcl-xL/Bcl-xS. Inhibiting Bcl-xL through splicing regulation can significantly enhance the radiation sensitivity of 2D and 3D GBM cells. These results suggested that manipulation of BCLX pre-mRNA alternative splicing by splice-switching oligonucleotides is a novel approach to inhibit glioblastoma tumorigenesis alone or in combination with radiotherapy.
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