CircLRFN5 inhibits the progression of glioblastoma via PRRX2/GCH1 mediated ferroptosis

Journal of Experimental & Clinical Cancer Research, Год журнала: 2022, Номер 41(1)

Опубликована: Окт. 20, 2022

Ferroptosis is a novel form of iron-dependent cell death and participates in the malignant progression glioblastoma (GBM). Although circular RNAs (circRNAs) are found to play key roles ferroptosis via several mechanisms, including regulating iron metabolism, glutathione lipid peroxidation mitochondrial-related proteins, there many circRNAs need be found, they may become new molecular treatment target GBM.The expression levels circLRFN5, PRRX2 GCH1 were detected by qPCR, western blotting, immunohistochemistry. Lentiviral-based infections used overexpress or knockdown these molecules glioma stem cells (GSCs). The biological functions on GSCs MTS (3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium), 5-ethynyl-20-deoxyuridine (EdU) incorporation assay, transwell, neurosphere formation assays, Extreme Limiting Dilution Analysis (ELDA) xenograft experiments. content was BODIPY 581/591 C11 (GSH) assay malondialdehyde (MDA) assay. mechanisms among studied RNA immunoprecipitation pull-down ubiquitination dual-luciferase reporter chromatin assay.We circRNA circLRFN5 downregulated GBM associated with patients' poor prognosis. CircLRFN5 overexpression inhibits viabilities, proliferation, neurospheres formation, stemness tumorigenesis inducing ferroptosis. Mechanistically, binds protein promotes its degradation ubiquitin-mediated proteasomal pathway. can transcriptionally upregulate GSCs, which suppressor generating antioxidant tetrahydrobiopterin (BH4).Our study as tumor-suppressive identified role GBM. potential biomarker for therapies ferroptosis-dependent therapy

Язык: Английский

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Exosomal circWDR62 promotes temozolomide resistance and malignant progression through regulation of the miR-370-3p/MGMT axis in glioma

Cell Death and Disease, Год журнала: 2022, Номер 13(7)

Опубликована: Июль 11, 2022

Exosome-mediated delivery of circular RNAs (circRNAs) is implicated in cancer progression. However, the role exosomal circRNAs chemotherapy resistance tumours remains poorly understood. Here we identified a novel circRNA, circWDR62. It was found that circWDR62 expression upregulated TMZ-resistant glioma cells and cell-derived exosomes compared with their controls by using high-throughput microarray analysis quantitative real-time polymerase chain reaction, high associated poor prognosis glioma. Functionally, downregulation could significantly inhibit TMZ malignant progression Further mechanistic studies showed plays sponging miR-370-3p as competing endogenous RNA. Rescue experiments confirmed MGMT downstream target circWDR62/miR-370-3p axis In addition, be transported between TMZ-sensitive via exosomes. Exosomal from conferred recipient sensitive while also enhancing proliferation, migration invasion these cells. A series clinical vivo trials corroborated promote chemoresistance Our results demonstrate for first time exosome-mediated can targeting miR-370-3p/MGMT vitro glioma, providing new therapeutic strategy. Moreover, human serum may serve promising prognostic marker therapy.

Язык: Английский

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The landscape of circRNAs in gliomas temozolomide resistance: Insights into molecular pathways

Non-coding RNA Research, Год журнала: 2024, Номер 9(4), С. 1178 - 1189

Опубликована: Май 21, 2024

As the deadliest type of primary brain tumor, gliomas represent a significant worldwide health concern. Circular RNA (circRNA), unique non-coding molecule, seems to be one most alluring target molecules involved in pathophysiology many kinds cancers. CircRNAs have been identified as prospective targets and biomarkers for diagnosis treatment numerous disorders, particularly malignancies. Recent research has established clinical link between temozolomide (TMZ) resistance certain circRNA dysregulations glioma tumors. may play therapeutic role controlling or overcoming TMZ provide guidance novel kind individualized therapy. To address biological characteristics circRNAs their potential induce TMZ, this review highlighted summarized possible roles that molecular pathways drug resistance, including Ras/Raf/ERK PI3K/Akt signaling pathway metabolic processes gliomas.

Язык: Английский

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Investigation of the Impact of Magnetic Resonance Imaging-assisted Surgery on Immune Cell Cytokine Levels and Efficacy in Patients with Gliomas

Current Problems in Surgery, Год журнала: 2024, Номер 63, С. 101640 - 101640

Опубликована: Окт. 18, 2024

Язык: Английский

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Hypoxia-Inducible Factor-Dependent and Independent Mechanisms Underlying Chemoresistance of Hypoxic Cancer Cells

Cancers, Год журнала: 2024, Номер 16(9), С. 1729 - 1729

Опубликована: Апрель 29, 2024

In hypoxic regions of malignant solid tumors, cancer cells acquire resistance to conventional therapies, such as chemotherapy and radiotherapy, causing poor prognosis in patients with cancer. It is widely recognized that some the key genes behind this are hypoxia-inducible transcription factors, e.g., factor 1 (HIF-1). Since HIF-1 activity suppressed by two representative 2-oxoglutarate-dependent dioxygenases (2-OGDDs), PHDs (prolyl-4-hydroxylases), FIH-1 (factor inhibiting 1), inactivation 2-OGDD has been associated therapy activation HIF-1. Recent studies have also revealed importance hypoxia-responsive mechanisms independent its isoforms (collectively, HIFs). article, we collate accumulated knowledge HIF-1-dependent responsible for anticancer drugs briefly discuss interplay between hypoxia responses, like EMT UPR, chemoresistance. addition, introduce a novel HIF-independent mechanism, which epigenetically mediated an acetylated histone reader protein, ATAD2, recently clarified.

Язык: Английский

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CircKPNB1 mediates a positive feedback loop and promotes the malignant phenotypes of GSCs via TNF-α/NF-κB signaling

Cell Death and Disease, Год журнала: 2022, Номер 13(8)

Опубликована: Авг. 9, 2022

Abstract Glioma stem cells (GSCs) are a special kind of in GBM showing tumor initiation, self-renewal, and multi-lineage differentiation abilities. Finding novel circRNAs related to GSCs is great significance for the study glioma. qPCR, western blotting, immunohistochemistry were used detect expression levels circKPNB1, SPI1, DGCR8, TNF-α. The these molecules was regulated by lentiviral-based infection. RNA immunoprecipitation assay, pull-down, dual-luciferase reporter, chromatin assays direct regulation mechanisms among molecules. All MTS, EDU, transwell, neurosphere formation assays, ELDA xenograft experiments malignant phenotype GSCs. We found circRNA circKPNB1 overexpressed associated with patients’ poor prognosis. CircKPNB1 overexpression can promote cell viabilities, proliferation, invasion, neurospheres abilities, stemness Mechanistically, regulates protein stability nuclear translocation SPI1. SPI1 promotes via TNF-α mediated NF-κB signaling. also transcriptionally upregulate DGCR8 expression, latter maintain forms positive feedback loop Our oncogene diagnosis prognosis prediction maybe target molecular targeted therapy.

Язык: Английский

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Epigenetic alterations in glioblastomas: Diagnostic, prognostic and therapeutic relevance

International Journal of Cancer, Год журнала: 2022, Номер 153(3), С. 476 - 488

Опубликована: Дек. 7, 2022

Abstract Glioblastoma, the most common and heterogeneous tumor affecting brain parenchyma, is dismally characterized by a very poor prognosis. Thus, search of new, more effective treatments vital need. Here, we will review druggable epigenetic features glioblastomas that are, indeed, currently explored in preclinical studies clinical trials for development effective, personalized treatments. In detail, have led to identification signatures, IDH mutations, MGMT gene methylation, histone modification alterations, H3K27 mutations epitranscriptome landscapes glioblastomas, each case discussing corresponding targeted therapies their potential efficacy. Finally, emphasize how recent technological improvements permit routinely investigate many glioblastoma biomarkers practice, further enforcing hope drugs, targeting specific features, could be future therapeutic option selected patients.

Язык: Английский

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The role of lncRNAs in the interplay of signaling pathways and epigenetic mechanisms in glioma

Epigenomics, Год журнала: 2025, Номер 17(2), С. 125 - 140

Опубликована: Янв. 19, 2025

Gliomas, highly aggressive tumors of the central nervous system, present overwhelming challenges due to their heterogeneity and therapeutic resistance. Glioblastoma multiforme (GBM), most malignant form, underscores this clinical urgency dismal prognosis despite treatment regimens. Recent advances in cancer research revealed signaling pathways epigenetic mechanisms that intricately govern glioma progression, offering multifaceted targets for intervention. This review explores dynamic interplay between events regulation context glioma, with a particular focus on crucial roles played by non-coding RNAs (ncRNAs). Through direct indirect targeting, ncRNAs emerge as key regulators shaping molecular landscape glioblastoma across its various stages. By dissecting these intricate regulatory networks, novel patient-tailored strategies could be devised improve patient outcomes devastating disease.

Язык: Английский

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RNA‐Seq Reveals the Mechanism of Synergistic Hydrogen‐Chemotherapy Based on Active Magnesium Micromotors for Inhibiting Glioblastoma Recurrence by Modulating Tumor Microenvironment

Small, Год журнала: 2025, Номер unknown

Опубликована: Апрель 21, 2025

Abstract Postoperative recurrence of glioblastoma (GBM) is a key contributing factor to the unfavorable prognosis patients. Chemotherapy has been extensively employed as postoperative treatment for GBM; however, produced drug resistance significantly undermines chemotherapeutic efficacy. Herein, multifunctional system based on magnesium micromotor (Mg‐Motor‐DOX) designed and fabricated that can generate hydrogen gas in situ actively deliver doxorubicin (DOX). Utilizing temperature‐sensitive hydrogel, Mg‐Motor‐DOX administrated residual cavity tumor after subtotal GBM resection. The H 2 by Mg‐water reaction not only propels motion motors but also functions an antioxidant effectively alleviate neuroinflammation caused bubbles create pronounced vortex flow situ, greatly enhancing DOX penetration sensitivity cells DOX. Therefore, synergistic hydrogen‐chemotherapy inhibits model. RNA‐Seq technology further elucidates role strategy modulating immune microenvironment via converting cold tumors into hot tumors, thereby establishing theoretical foundation clinical implementation hydrogen‐chemotherapy.

Язык: Английский

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Tumor heterogeneity and resistance in glioblastoma: the role of stem cells

APOPTOSIS, Год журнала: 2025, Номер unknown

Опубликована: Май 15, 2025

Язык: Английский

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