ArticleJournal of experimental & clinical cancer research : CR2018
Alternative splicing of human telomerase reverse transcriptase in gliomas and its modulation mediated by CX-5461.
Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 36 citations in OpenAlex.
- Structural insights into the binding of CX-5461 and MTR-106 to G-quadruplex DNA.Nucleic acids research · 2026Article
- BLM and FANCJ role in the response to G-quadruplex-dependent telomeric replicative stress.Communications biology · 2026Article
- The G-quadruplex ligand CX-5461: an innovative candidate for disease treatment.Journal of translational medicine · 2025Review
- Genetic regulation of TERT splicing affects cancer risk by altering cellular longevity and replicative potential.Nature communications · 2025Article
- Genetic regulation ofmedRxiv : the preprint server for health sciences · 2024Article
- The Role of Glia Telomere Dysfunction in the Pathogenesis of Central Nervous System Diseases.Molecular neurobiology · 2024Review
- Article
- Isocitrate dehydrogenase wt and IDHmut adult-type diffuse gliomas display distinct alterations in ribosome biogenesis and 2'O-methylation of ribosomal RNA.Neuro-oncology · 2023Article
- Combining old and new concepts in targeting telomerase for cancer therapy: transient, immediate, complete and combinatory attack (TICCA).Cancer cell international · 2023Review
- How does precursor RNA structure influence RNA processing and gene expression?Bioscience reports · 2023Review
- Spotlight onGenes · 2023Article
- Establishment and characterization of an immortalized bovine intestinal epithelial cell line.Journal of animal science · 2023Article
- N6-methyladenosine RNA methylation regulator-related alternative splicing gene signature as prognostic predictor and in immune microenvironment characterization of patients with low-grade glioma.Frontiers in genetics · 2022Article
- Landscape of Alternative Splicing Events Related to Prognosis and Immune Infiltration in Glioma: A Data Analysis and Basic Verification.Journal of immunology research · 2022Article
- New phase therapeutic pursuits for targeted drug delivery in glioblastoma multiforme.Exploration of targeted anti-tumor therapy · 2022Review
- Noncanonical Role of Telomerase in Regulation of Microvascular Redox Environment With Implications for Coronary Artery Disease.Function (Oxford, England) · 2022Article
- G-quadruplex DNA: a novel target for drug design.Cellular and molecular life sciences : CMLS · 2021Review
- Alternative Splicing of Human Telomerase Reverse Transcriptase (hTERT) and Its Implications in Physiological and Pathological Processes.Biomedicines · 2021Review
- Telomerase Regulation: A Role for Epigenetics.Cancers · 2021Review
- Characterization and prognostic significance of alternative splicing events in lower-grade diffuse gliomas.Journal of cellular and molecular medicine · 2020Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundGlioma is a heterogeneous, invasive primary brain tumor with a wide range of patient survival and a lack of reliable prognostic biomarkers. Human telomerase reverse transcriptase (hTERT) has been reported in the presence of multiple transcripts in various tumor systems. The biological function and precise regulatory mechanisms of hTERT transcripts remain uncertain.
methodsAlternative splicing of hTERT and telomerase activity were examined in 96 glioma specimens, including 38 glioblastomas (GBMs), 23 oligodendrogliomas (ODMs), and 35 oligoastrocytomas (OAMs). The correlation between telomerase activity or hTERT transcripts and patient clinical characteristics was investigated. We examined the regulation of alternative splicing of hTERT and telomerase activity by G-quadruplex stabilizer CX-5461 in GBM cells. The biological effects of CX-5461 on GBM cell lines, including inhibition of cell proliferation, effects on cell cycle/apoptosis, and telomere DNA damage were further explored.
resultsThe β splicing was verified in human gliomas and hTERT+β was significantly correlated with higher telomerase activity, higher KPS, larger tumor size, and higher tumor grades. Meanwhile, glioma patients lacking hTERT+β expression or telomerase activity showed a significant survival benefit. Notably, CX-5461 altered hTERT splicing patterns, leading to an increase of hTERT-β transcript and a decrease of hTERT+β transcript expression, which inhibits telomerase activity. In addition, CX-5461 had cytotoxic effects on GBM cells and caused telomere DNA damage response, induced G2/M arrest and apoptosis.
conclusionsThe hTERT+β is verified to be correlated with clinical parameters in gliomas, and could serve as a prognostic marker or possibly therapeutic target for gliomas. CX-5461 can regulate the splicing pattern of hTERT, inhibit telomerase activity, and kill GBM cells.
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