ArticleThe Journal of clinical investigation2014
miR-33a promotes glioma-initiating cell self-renewal via PKA and NOTCH pathways.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
55 citing papers in PubMed, 89 citations in OpenAlex.
- Targeting NOTCH-immune crosstalk in gliomas: from mechanisms to therapeutics.Frontiers in oncology · 2026Review
- Pan-Cancer Analysis of Cyclic Nucleotide Phosphodiesterases (PDEs) Expression, Variation, and Prognostic Significance.ACS omega · 2025Article
- Intertwined regulators: hypoxia pathway proteins, microRNAs, and phosphodiesterases in the control of steroidogenesis.Pflugers Archiv : European journal of physiology · 2024Review
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Tumor microenvironment of cancer stem cells: Perspectives on cancer stem cell targeting.Genes & diseases · 2024Review
- Use of microRNAs as Diagnostic, Prognostic, and Therapeutic Tools for Glioblastoma.International journal of molecular sciences · 2024Review
- Single-cell transcriptomic analysis identifies downregulated phosphodiesterase 8B as a novel oncogene in IDH-mutant glioma.Frontiers in immunology · 2024Article
- PERK-Mediated Cholesterol Excretion from IDH Mutant Glioma Determines Anti-Tumoral Polarization of Microglia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Review
- HES1-mediated down-regulation of miR-138 sustains NOTCH1 activation and promotes proliferation and invasion in renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2023Article
- Dedifferentiated cells obtained from glioblastoma cell lines are an easy and robust model for mesenchymal glioblastoma stem cells studies.American journal of cancer research · 2023Article
- Non-coding RNAs and glioma: Focus on cancer stem cells.Molecular therapy oncolytics · 2022Review
- Recent insights into the microRNA-dependent modulation of gliomas from pathogenesis to diagnosis and treatment.Cellular & molecular biology letters · 2022Review
- FOSL1 promotes proneural-to-mesenchymal transition of glioblastoma stem cells via UBC9/CYLD/NF-κB axis.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- GABAMolecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- MiR-33a targets FOSL1 and EN2 as a clinical prognostic marker for sarcopenia by glioma.Frontiers in genetics · 2022Article
- The effectiveness of plasma miR-33a-5p as a predictive biomarker for the efficacy of colorectal cancer chemotherapy.Oncology letters · 2021Article
- Hypoxia Transcriptomic Modifications Induced by Proton Irradiation in U87 Glioblastoma Multiforme Cell Line.Journal of personalized medicine · 2021Article
- Structure, regulatory factors and cancer-related physiological effects of ADAM9.Cell adhesion & migration · 2020Review
- Complex roles of cAMP-PKA-CREB signaling in cancer.Experimental hematology & oncology · 2020Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Glioblastoma (GBM) is the most common and lethal brain tumor in adults. Glioma-initiating cells (GICs) are stem-like cells that have been implicated in glioblastoma progression and recurrence; however, the distinct properties of GICs and non-GICs within GBM tumors are largely uncharacterized. Here, we evaluated stem cell-associated microRNA (miR) expression in GICs from GBM patients and GICs derived from xenografted human glioma cell lines and determined that miR-33a promotes GIC growth and self-renewal. Moreover, evaluation of a GBM tissue array revealed that higher miR-33a expression was associated with poor prognosis of GBM patients. Antagonizing miR-33a function in GICs reduced self-renewal and tumor progression in immune-compromised mice, whereas overexpression of miR-33a in non-GICs promoted the display of features associated with GICs. We identified the mRNAs encoding phosphodiesterase 8A (PDE8A) and UV radiation resistance-associated gene (UVRAG) as direct miR-33a targets. PDE8A and UVRAG negatively regulated the cAMP/PKA and NOTCH pathways, respectively; therefore, miR-33a-dependent reduction of these proteins promoted growth and self-renewal of GICs by enhancing PKA and NOTCH activity. Furthermore, in GBM specimens, there was an inverse correlation between the expression levels of miR-33a and PDE8A and UVRAG expression. These findings reveal a miR-33a-centered signaling network that promotes GIC maintenance and has potential as a therapeutic target for GBM treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.