Multiple therapeutic approaches of glioblastoma multiforme: From terminal to therapy

Kumari, Smita; Gupta, Rohan; Ambasta, Rashmi K.; Kumar, Pravir

doi:10.1016/j.bbcan.2023.188913

Cited by 9 publications

(4 citation statements)

References 413 publications

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“…Glioblastoma, as a malignant tumor, has a poor prognosis despite possessing a favorable methylation profile. This is due to the strong proliferation of glioma cells and high infiltration in the brain, which leads to the failure of localized treatment [ 43 ]. Therefore, controlling the proliferation of glioma cells and reducing their invasiveness has become an important research direction.…”

Section: Discussionmentioning

confidence: 99%

LINC00606 promotes glioblastoma progression through sponge miR-486-3p and interaction with ATP11B

Dong,

Qi,

et al. 2024

J Exp Clin Cancer Res

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Background LncRNAs regulate tumorigenesis and development in a variety of cancers. We substantiate for the first time that LINC00606 is considerably expressed in glioblastoma (GBM) patient specimens and is linked with adverse prognosis. This suggests that LINC00606 may have the potential to regulate glioma genesis and progression, and that the biological functions and molecular mechanisms of LINC00606 in GBM remain largely unknown. Methods The expression of LINC00606 and ATP11B in glioma and normal brain tissues was evaluated by qPCR, and the biological functions of the LINC00606/miR-486-3p/TCF12/ATP11B axis in GBM were verified through a series of in vitro and in vivo experiments. The molecular mechanism of LINC00606 was elucidated by immunoblotting, FISH, RNA pulldown, CHIP-qPCR, and a dual-luciferase reporter assay. Results We demonstrated that LINC00606 promotes glioma cell proliferation, clonal expansion and migration, while reducing apoptosis levels. Mechanistically, on the one hand, LINC00606 can sponge miR-486-3p; the target gene TCF12 of miR-486-3p affects the transcriptional initiation of LINC00606, PTEN and KLLN. On the other hand, it can also regulate the PI3K/AKT signaling pathway to mediate glioma cell proliferation, migration and apoptosis by binding to ATP11B protein. Conclusions Overall, the LINC00606/miR-486-3p/TCF12/ATP11B axis is involved in the regulation of GBM progression and plays a role in tumor regulation at transcriptional and post-transcriptional levels primarily through LINC00606 sponging miR-486-3p and targeted binding to ATP11B. Therefore, our research on the regulatory network LINC00606 could be a novel therapeutic strategy for the treatment of GBM. Graphical Abstract LINC00606 is highly expressed in GBM patients with carcinogenic function and correlated with poor prognosis. LINC00606 regulates glioblastoma progression by sponging miR-486-3p and interacting with ATP11B.

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Section: Discussionmentioning

confidence: 99%

LINC00606 promotes glioblastoma progression through sponge miR-486-3p and interaction with ATP11B

Dong,

Qi,

et al. 2024

J Exp Clin Cancer Res

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“…Glioblastoma multiforme (GBM) remains an enigma in the annals of oncology [36][37][38][39] , presenting as an aggressive malignancy with multifactorial determinants that circumvent the effectiveness of many therapeutic interventions [40][41][42][43][44] . In our pursuit to understand the intricate molecular and epigenetic mechanisms underlying GBM's notorious resistance to TMZ, we delved into the cross-talk between MGMT promoter methylation histone modi cation (particularly H3K9ac), and the transcriptional milieu led by SP1.…”

Section: Discussionmentioning

confidence: 99%

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

Ye,

Gu,

Wang

et al. 2023

Preprint

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

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“… 5 , 6 , 7 In the treatment of gliomas, surgical resection with maximum safety, radiation therapy, and chemotherapy with temozolomide (TMZ) are the main recommendations for patients in good physical condition. 8 , 9 The goals of surgical treatment are to clarify the pathologic diagnosis, reduce tumor volume, decrease tumor cell count, improve symptoms, relieve hypercapnic pressure symptoms, prolong life, and create time for other subsequent comprehensive treatments. However, due to the proliferative nature of gliomas, they cannot be completely removed by surgery and are prone to recurrence after surgery.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticles for efficient drug delivery and drug resistance in glioma: New perspectives

Liu,

Yang,

et al. 2024

CNS Neurosci Ther

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Gliomas are the most common primary tumors of the central nervous system, with glioblastoma multiforme (GBM) having the highest incidence, and their therapeutic efficacy depends primarily on the extent of surgical resection and the efficacy of postoperative chemotherapy. The role of the intracranial blood–brain barrier and the occurrence of the drug‐resistant gene O6‐methylguanine‐DNA methyltransferase have greatly limited the efficacy of chemotherapeutic agents in patients with GBM and made it difficult to achieve the expected clinical response. In recent years, the rapid development of nanotechnology has brought new hope for the treatment of tumors. Nanoparticles (NPs) have shown great potential in tumor therapy due to their unique properties such as light, heat, electromagnetic effects, and passive targeting. Furthermore, NPs can effectively load chemotherapeutic drugs, significantly reduce the side effects of chemotherapeutic drugs, and improve chemotherapeutic efficacy, showing great potential in the chemotherapy of glioma. In this article, we reviewed the mechanisms of glioma drug resistance, the physicochemical properties of NPs, and recent advances in NPs in glioma chemotherapy resistance. We aimed to provide new perspectives on the clinical treatment of glioma.

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Multiple therapeutic approaches of glioblastoma multiforme: From terminal to therapy

Cited by 9 publications

References 413 publications

LINC00606 promotes glioblastoma progression through sponge miR-486-3p and interaction with ATP11B

LINC00606 promotes glioblastoma progression through sponge miR-486-3p and interaction with ATP11B

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

Nanoparticles for efficient drug delivery and drug resistance in glioma: New perspectives

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