ArticleCancer science2021
Heparanase confers temozolomide resistance by regulation of exosome secretion and circular RNA composition in glioma.
Article in Cancer science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 41 citations in OpenAlex.
- The emerging role of exosomal circRNAs in modulating apoptotic pathways and overcoming cancer therapy resistance.Discover oncology · 2026Review
- The Transcriptional Role of Circular RNAs in Drug Resistance by Modulating the miRNA/mRNA Axis.Experientia supplementum (2012) · 2026Article
- Diagnostic and therapeutic potential of exosomal circRNAs in cancer: decoding the circular code toward precision medicine.Cancer cell international · 2025Review
- T Cell Activation Induces Synthesis of CD47 Proteoglycan Isoforms and Their Release in Extracellular Vesicles.International journal of molecular sciences · 2025Article
- The Role of Circular RNA in the Progression of Gliomas and Its Potential Clinical Applications.Biology · 2025Review
- Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights.Acta neuropathologica communications · 2025Review
- Exosome-Mediated Chemoresistance in Cancers: Mechanisms, Therapeutic Implications, and Future Directions.Biomolecules · 2025Review
- Exosomal circRNAs: Deciphering the novel drug resistance roles in cancer therapy.Journal of pharmaceutical analysis · 2025Review
- Role of Non-coding RNAs in the Response of Glioblastoma to Temozolomide.Molecular neurobiology · 2025Review
- Regulatory role of circular RNAs in the development of therapeutic resistance in the glioma: A double-edged sword.Iranian journal of basic medical sciences · 2025Review
- The landscape of circRNAs in gliomas temozolomide resistance: Insights into molecular pathways.Non-coding RNA research · 2024Review
- Circular RNAs in human diseases.MedComm · 2024Review
- From bench to bedside: The promising value of exosomes in precision medicine for CNS tumors.Heliyon · 2024Review
- Hypoxia-induced activation of HIF-1alpha/IL-1beta axis in microglia promotes glioma progression via NF-κB-mediated upregulation of heparanase expression.Biology direct · 2024Article
- Hsa_circ_0001359 in Serum Exosomes: A Promising Marker to Predict Bronchopulmonary Dysplasia in Premature Infants.Journal of inflammation research · 2024Article
- Kaempferol and Biomodified Kaempferol fromInternational journal of molecular sciences · 2023Article
- The Dual Effects of Exosomes on Glioma: A Comprehensive Review.Journal of Cancer · 2023Review
- Exosomal circRNAs as promising liquid biopsy biomarkers for glioma.Frontiers in immunology · 2023Review
- Regulatory mechanisms and clinical applications of tumor-driven exosomal circRNAs in cancers.International journal of medical sciences · 2023Review
- Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Temozolomide (TMZ) resistance is the main challenge in the management of glioma patients. Heparanase can mediate the secretion and function of exosomes, which are considered to be a promising molecular delivery system for cancer therapy. Therefore, this study aimed to investigate whether heparanase-mediated delivery of exosomes was related to TMZ resistance of glioma. Heparanase was upregulated in TMZ-resistant glioma cells, and overexpression of heparanase led to increased resistance of U87 cells to TMZ. Knockdown of heparanase led to increased sensitivity of TMZ-resistant U251 cells (U251R) cells to TMZ. Heparanase promoted the secretion of exosomes from glioma cells, and coculture with exosomes derived from heparanase knockdown U251R cells partly restored the sensitivity of U251 cells to TMZ compared with exosomes derived from si-control transfected U251R cells. It was identified by circular RNA microarrays that hsa_circ_0042003 was upregulated in exosomes derived from U251R, which could be positively regulated by heparanase. U251R cell-derived exosomal hsa_circ_0042003 conferred the resistance of U251 cells to TMZ. In vivo studies also showed that U251R cell-derived exosomes induced resistance of U251 cells to TMZ, and the combination of tail-injected exosomal si-heparanase or exosomal si-hsa_circ_0042003 and intraperitoneal TMZ applied to nude mice abolished TMZ resistance. Heparanase mediated the transfer of exosomal hsa_circ_0042003 from TMZ-resistant glioma cells to drug-sensitive cells, which contributed to the chemoresistance of glioma to TMZ.
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Registered trials
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