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

Non-coding RNA Research, Journal Year: 2024, Volume and Issue: 9(4), P. 1178 - 1189

Published: May 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.

Language: Английский

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Identification of TMZ resistance‐associated histone post‐translational modifications in glioblastoma using multi‐omics data

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(3)

Published: March 1, 2024

Abstract Backgroud Glioblastoma multiforme (GBM) is among the most aggressive cancers, with current treatments limited in efficacy. A significant hurdle treatment of GBM resistance to chemotherapeutic agent temozolomide (TMZ). The methylation status MGMT promoter has been implicated as a critical biomarker response TMZ. Methods To explore mechanisms underlying resistance, we developed two TMZ‐resistant cell lines through gradual increase TMZ exposure. Transcriptome sequencing revealed that alterations histone post‐translational modifications might be instrumental conferring resistance. Subsequently, multi‐omics analysis suggests strong association between H3 lysine 9 acetylation (H3K9ac) levels and Results We observed correlation expression H3K9ac MGMT, particularly unmethylated samples. More importantly, our findings suggest may enhance transcription by facilitating recruitment SP1 factor binding site. Additionally, analyzing single‐cell transcriptomics data from matched primary recurrent tumors treated TMZ, modeled molecular shifts occurring upon tumor recurrence. also noted reduction stem characteristics, accompanied an H3K9ac, SP1, levels, underscoring potential role relapse following therapy. Conclusions appears its sites within locus, consequently upregulating driving GBM.

Language: Английский

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Long Non-Coding RNAs in Malignant Human Brain Tumors: Driving Forces Behind Progression and Therapy

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 694 - 694

Published: Jan. 15, 2025

Long non-coding RNAs (lncRNAs) play a pivotal role in regulating gene expression and are critically involved the progression of malignant brain tumors, including glioblastoma, medulloblastoma, meningioma. These lncRNAs interact with microRNAs (miRNAs), proteins, DNA, influencing key processes such as cell proliferation, migration, invasion. This review highlights multifaceted impact lncRNA dysregulation on tumor underscores their potential therapeutic targets to enhance efficacy chemotherapy, radiotherapy, immunotherapy. The insights provided offer new directions for advancing basic research clinical applications tumors.

Language: Английский

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Post-Marketing Safety of Temozolomide: A Pharmacovigilance Study Based on the Food and Drug Administration Adverse Event Reporting System

Oncology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 9

Published: Jan. 24, 2025

Introduction: Temozolomide (TMZ) is a widely used chemotherapy agent for the treatment of malignant gliomas and other brain tumors. Despite its established therapeutic benefits, there an ongoing need to understand better safety profile, particularly in real-world clinical settings. This study aimed identify critical adverse drug reactions (ADRs) associated with TMZ by utilizing FDA Adverse Event Reporting System (FAERS) database, thereby providing valuable insights practice. Methods: We utilized reported odds ratio, proportional reporting Bayesian Confidence Propagation Neural Network, Empirical Bayes Geometric Mean as primary algorithms disproportionality analysis. events (AEs) were classified ADRs only upon meeting criteria set all four algorithms. To ensure accuracy our results, we meticulously excluded any AEs deemed unrelated TMZ. Results: From October 2003 September 2023, total 10,502,538 case reports 9,073 cases explicitly attributed retrieved from FAERS database. After applying filters, 116 ADRs, each corresponding Preferred Term (PT), identified across 18 Organ Classes (SOCs). The primarily involved bone marrow suppression, hepatotoxicity, various infections, notably Pneumocystis jirovecii pneumonia. Furthermore, analysis not listed label, including congenital, familial, genetic disorders at SOC level, well unexpected PT such seizures, pulmonary embolism, sepsis. Conclusion: pharmacovigilance has significant previously unreported Further research validation resolution urgently needed guide application TMZ, ensuring efficacy use treating

Language: Английский

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The epigenetic mechanisms involved in the treatment resistance of glioblastoma

Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Glioblastoma (GBM) is an aggressive malignant brain tumor with almost inevitable recurrence despite multimodal management surgical resection and radio-chemotherapy. While several genetic, proteomic, cellular, anatomic factors interplay to drive promote treatment resistance, the epigenetic component remains among most versatile heterogeneous of these factors. Herein, landscape GBM refers a myriad modifications processes that can alter gene expression without altering genetic code cancer cells. These encompass DNA methylation, histone modification, chromatin remodeling, non-coding RNA molecules, all which have been found be implicated in augmenting tumor’s behavior driving its resistance therapeutics. This review aims delve into underlying interactions mediate this role for each components. Further, it discusses two-way relationship between heterogeneity plasticity, are crucial effectively treat GBM. Finally, we build on previous characterization explore specific targets investigated development promising therapeutic agents.

Language: Английский

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Nanofibers in Glioma Therapy: Advances, Applications, and Overcoming Challenges

International Journal of Nanomedicine, Journal Year: 2025, Volume and Issue: Volume 20, P. 4677 - 4703

Published: April 1, 2025

Despite relentless effort to study glioma treatment, the prognosis for patients remains poor. The main obstacles include high rate of recurrence and difficulty passing blood-brain barrier (BBB) therapeutic drugs. Nanomaterials owing their special physicochemical properties have been used in a wide range fields thus far. nanodrug delivery system (NDDS) with ability crossing BBB, targeting site, maintaining drug stability controlling release, has significantly enhanced anti-tumor effect, improving patients. Aligned nanofibers (NFs) are ideal materials establish vitro models microenvironment (GME), enabling exploration mechanism cell migration invasion discover novel targets. Moreover, NFs now widely applications such as radiotherapy, phototherapy, thermotherapy immunotherapy. absolute dominance anti-glioma applications, there still some problems further optimization NDDS, impact interactions between protein corona (PC) on therapy. This paper will shed light latest systems mimicking tumor (TME), discuss how optimize NDDS eliminate or utilize nanomedicine-PC interactions.

Language: Английский

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The importance of the circRNA/Wnt axis in gliomas: biological functions and clinical opportunities

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 261, P. 155510 - 155510

Published: July 31, 2024

Language: Английский

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Lentinan Regulates Glioma Cell Proliferation and Apoptosis by Activating p53 and Caspases Pathways

Pharmacognosy Magazine, Journal Year: 2024, Volume and Issue: 20(4), P. 1154 - 1166

Published: May 16, 2024

Background Gliomas are highly lethal malignancies that develop in the central nervous system. The primary treatment for gliomas involves surgical resection followed by chemoradiotherapy. However, due to infiltrative growth nature of gliomas, is often incomplete. Moreover, efficacy chemotherapeutic drugs constrained their ability cross blood–brain barrier, and currently utilized agents can lose effectiveness, particularly with prolonged administration. Lentinan, an active compound Lentinula edodes, exhibits various pharmacological activities. Purpose This study aims investigate anti-tumor effects lentinan on glioma U251 cells. Materials Methods Cell proliferation assays, cell fluorescence staining, scratch healing experiments, transwell chamber experiments were conducted assess activity Additionally, quantitative real-time polymerase chain reaction (qPCR) Western blot performed validate mechanism lentinan. Results findings revealed significantly suppressed cells, induced robust apoptosis, decreased cells’ migration invasion capabilities. Furthermore, notably influenced gene protein expression p53, Bcl-2, Cyto-c, Bax, Caspases, MMP-9 Conclusion These suggest may inhibit cells activating P53 caspase-related apoptosis pathways.

Language: Английский

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Bibliometric and visualization analysis in the field of epigenetics and glioma (2009–2024)

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Oct. 29, 2024

Glioma represents the most prevalent primary malignant tumor in central nervous system, a deeper understanding of underlying molecular mechanisms driving glioma is imperative for guiding future treatment strategies. Emerging evidence has implicated close relationship between development and epigenetic regulation. However, there remains significant lack comprehensive summaries this domain. This study aims to analyze publications pertaining gliomas from 2009 2024 using bibliometric methods, consolidate extant research, delineate prospects investigation critical area.

Language: Английский

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Unraveling the Role of Transcription Factor SP1 and H3K9 Acetylation in MGMT Regulation and Temozolomide Resistance in Glioblastoma Multiforme

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 9, 2023

Abstract Glioblastoma multiforme (GBM) is recognized as a highly aggressive brain tumor, exhibiting profound resistance to temozolomide (TMZ) chemotherapy. While methylation of the MGMT promoter has been identified significant factor determining response TMZ, recent evidence indicates that regulatory mechanisms are multifaceted, involving complex interplays with broader epigenetic and transcriptional landscapes. In this study, we meticulously developed TMZ-resistant GBM cell lines applied comprehensive suite analytical methodologies, including transcriptomic proteomic analyses, single-cell profiling, elucidate molecular complexities associated TMZ resistance. Our results demonstrate crucial correlation between increased levels H3K9 acetylation (H3K9ac), elevated expression, heightened resistance, remains steadfast even in methylated promoters. Simultaneously, transcription SP1 key regulator, synergizing H3K9ac orchestrate transcription. Single-cell analysis revealed subtle expression discrepancies among subpopulations, propensity for pathway activity predominantly mesenchymal subtype. As tumors relapsed, documented transformation cellular character GBM, migrating from stem-like state differentiation. This transition marked by progressive upregulation MGMT, SP1, H3K9ac. These findings suggest while clinical relevance undeniable, understanding necessitates focus on synergy histone modifications, regulations, diversity. By deconstructing these intricate relationships, research enhances our comprehension inherent resilience TMZ.

Language: Английский

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