Cholesterol metabolism and its implication in glioblastoma therapy

Guo, Xuyang; Zhou, Shaolong; Yang, Zhuo; Li, Zian; Hu, Weihua; Dai, Lirui; Liang, Wulong; Wang, Xinjun

doi:10.7150/jca.63609

Cited by 20 publications

(14 citation statements)

References 98 publications

(104 reference statements)

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“…The reprogramming of lipid and cholesterol metabolism has been linked to many cancers, including GBM, while GBM cell growth is highly dependent on cholesterol. Oxysterols, such as 7-ketocholesterol, are oxidized forms of cholesterol that participate in the regulation of cholesterol metabolism through liver X receptors (LXRs) and sterol regulatory element-binding proteins (SREBPs) [ 61 , 62 , 63 , 64 ]. SREBPs are highly upregulated in GBM.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the feedback loop of miR-29-SCAP/SREBP-1 modulates GBM growth, which is driven by EGFR signaling via the regulation of cholesterol synthesis [ 65 , 66 ]. Oxysterols have been also reported to have antitumor activity in GBM by activating LXRs, thus disrupting cholesterol homeostasis [ 62 ]. Our mixed-methods content analysis revealed no output for 2-acetyl-4-methylpyridine, piperidine, and 3-(4-methyl-3pentenyl) thiophene or hippuric acid.…”

Section: Discussionmentioning

confidence: 99%

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Bioenergetic Profiling in Glioblastoma Multiforme Patients with Different Clinical Outcomes

et al. 2023

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The accumulation of cell biomass is associated with dramatically increased bioenergetic and biosynthetic demand. Metabolic reprogramming, once thought as an epiphenomenon, currently relates to disease progression, also in response to extracellular fate-decisive signals. Glioblastoma multiforme patients often suffer misdiagnosis, short survival time, low quality of life, and poor disease management options. Today, tumor genetic testing and histological analysis guide diagnosis and treatment. We and others appreciate that metabolites complement translational biomarkers and molecular signatures in disease profiling and phenotyping. Herein, we coupled a mixed-methods content analysis to a mass spectrometry-based untargeted metabolomic analysis on plasma samples from glioblastoma multiforme patients to delineate the role of metabolic remodeling in biological plasticity and, hence, disease severity. Following data processing and analysis, we established a bioenergetic profile coordinated by the mitochondrial function and redox state, lipids, and energy substrates. Our findings show that epigenetic modulators are key players in glioblastoma multiforme cell metabolism, in particular when microRNAs are considered. We propose that biological plasticity in glioblastoma multiforme is a mechanism of adaptation and resistance to treatment which is eloquently revealed by bioenergetics.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bioenergetic Profiling in Glioblastoma Multiforme Patients with Different Clinical Outcomes

et al. 2023

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“…Due to the discovery that many cancers, including GBM, reprogrammed cholesterol metabolism, cholesterol metabolism has become a promising potential target for therapy. As GBM cells require external cholesterol for survival, as well as lipid droplets for rapid growth, different strategies have been proposed to inhibit cholesterol metabolism, including inhibition of cholesterol uptake and promotion of cholesterol efflux by activating liver X receptors (LXRs), disruption of cellular cholesterol trafficking, inhibition of SREBP signaling, inhibition of cholesterol esterification, and may potentially counteract with glial tumor growth [109,110]. There is an association between obesity-related pathologies of the central nervous system (CNS) like neuroinflammation and reactive gliosis and a high-fat diet (HFD)-related elevation of saturated fatty acids like palmitic acid (PA) in neurons and astrocytes of the brain.…”

Section: Discussionmentioning

confidence: 99%

Integrating Multi-Omics Analysis for Enhanced Diagnosis and Treatment of Glioblastoma: A Comprehensive Data-Driven Approach

Behrooz¹,

Latifi-Navid²,

Rosa³

et al. 2023

Preprint

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The most aggressive primary malignant brain tumor in adults is glioblastoma (GBM), which has poor overall survival (OS). There is a high relapse rate among patients with GBM despite maxi-mally safe surgery, radiation therapy, temozolomide (TMZ), and aggressive treatment. Hence, there is an urgent and unmet clinical need for new approaches to managing GBM. The current study identified modules (MYC, EGFR, PIK3CA, SUZ12, and SPRK2) involved in GBM disease through the NeDRex plugin. Furthermore, hub genes were identified in a comprehensive interaction network containing 7,560 proteins related to GBM disease and 3,860 proteins associated with signaling pathways involved in GBM. By integrating the results of the aforementioned analyses and performing centrality analysis again, eleven key genes involved in GBM disease were identi-fied. ProteomicsDB or Gliovis databases were used for determining the gene expression in normal or tumor brain tissue. The NetworkAnalyst and the mGWAS-Explorer tools identified miRNAs, SNPs, and metabolites associated with these 11 genes. Moreover, a literature review of recent studies revealed other lists of metabolites related to GBM disease. The enrichment analysis of iden-tified genes, miRNAs, and metabolites associated with GBM disease was done using ExpressAna-lyst, miEAA, and MetaboAnalyst tools. Further investigation of metabolite roles in GBM was done through the pathway, joint pathway, and network analyses. The results of this study identified 11 genes (UBC, HDAC1, CTNNB1, TRIM28, CSNK2A1, RBBP4, TP53, APP, DAB1, PINK1, and RELN), five miRNAs (hsa-mir-221-3p, hsa-mir-30a-5p, hsa-mir-15a-5p, hsa-mir-130a-3p, hsa-let-7b-5p), six metabolites (HDL, N6-acetyl-L-lysine, cholesterol, formate, N, N-dimethylglycine/xylose and X2. piperidinone) and 15 distinct signaling pathways that play an indispensable role in the GBM disease development. To establish early diagnostic methods and plan personalized GBM treatment strategies, the identified top genes-miRNAs and metabolite signatures can be targeted.

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“…According to research, glioma cells may convert cholesterol into corticosteroids like progesterone, androstenedione, androstenediol, and androstenedione, which may speed up glioma progression [ 46 ]. Apo-E-carrying cholesterol is endocytosed by neurons, which are specialized in producing electrical activity and rely on adjacent astrocytes to transport cholesterol [ 47 ].…”

Section: Introductionmentioning

confidence: 99%

The effects of statin therapy on brain tumors, particularly glioma: a review

Alrosan,

Heilat,

Al Subeh

et al. 2023

Anti-Cancer Drugs

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Brain tumors account for less than 2% of all malignancies. However, they are associated with the highest morbidity and mortality rates among all solid tumors. The most common malignant primary brain tumors are glioma or glioblastoma (GBM), which have a median survival time of about 14 months, often suffer from recurrence after a few months following treatment, and pose a therapeutic challenge. Despite recent therapeutic advances, the prognosis for glioma patients is poor when treated with modern therapies, including chemotherapy, surgery, radiation, or a combination of these. Therefore, discovering a new target to treat brain tumors, particularly glioma, might be advantageous in raising progression-free survival and overall survival (OS) rates. Statins, also known as competitive HMG-CoA reductase inhibitors, are effective medications for reducing cholesterol and cardiovascular risk. The use of statins prior to and during other cancer treatments appears to enhance patient outcomes according to preclinical studies. After surgical resection followed by concurrent radiation and treatment, OS for patients with GBM is only about a year. Statins have recently emerged as potential adjuvant medications for treating GBM due to their ability to inhibit cell growth, survival, migration, metastasis, inflammation, angiogenesis, and increase apoptosis in-vitro and in-vivo studies. Whether statins enhance clinical outcomes, such as patient survival in GBM, is still debatable. This study aimed to explore the effects of statin therapy in the context of cancer treatment, with a particular focus on GBM.

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Cholesterol metabolism and its implication in glioblastoma therapy

Cited by 20 publications

References 98 publications

Bioenergetic Profiling in Glioblastoma Multiforme Patients with Different Clinical Outcomes

Bioenergetic Profiling in Glioblastoma Multiforme Patients with Different Clinical Outcomes

Integrating Multi-Omics Analysis for Enhanced Diagnosis and Treatment of Glioblastoma: A Comprehensive Data-Driven Approach

The effects of statin therapy on brain tumors, particularly glioma: a review

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