Development of a prognostic model based on an immunogenomic landscape analysis of medulloblastoma

Guo, Yunbo; Li, Shenglun; Huang, Peng; Zhang, Hongwei; Yu, Chunmei

doi:10.1042/bsr20202907

Cited by 5 publications

(4 citation statements)

References 71 publications

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“…As mentioned above, inositols can impair oncogenic signalling using several mechanisms including inhibition of the PI3K/Akt pathway 43 . Notably, this has already been recognised in medulloblastoma as one of the relevant oncogenic pathways contributing to the disease 53 and, accordingly, a selective pan-class I PI3K inhibitor namely BKM120 has been revealed as a potential novel therapy for MB 54 . Thus, in our MYC-driven cell models OTX-015 treatment may upregulate myo-inositol production, counteracting PI3K/Akt/mTOR signalling and eventually triggering tumour cell death.…”

Section: Discussionmentioning

confidence: 99%

Metabolic rewiring in MYC-driven medulloblastoma by BET-bromodomain inhibition

Graziani

Garcia

Alcolado

et al. 2023

Sci Rep

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Medulloblastoma (MB) is the most common malignant brain tumour in children. High-risk MB patients harbouring MYC amplification or overexpression exhibit a very poor prognosis. Aberrant activation of MYC markedly reprograms cell metabolism to sustain tumorigenesis, yet how metabolism is dysregulated in MYC-driven MB is not well understood. Growing evidence unveiled the potential of BET-bromodomain inhibitors (BETis) as next generation agents for treating MYC-driven MB, but whether and how BETis may affect tumour cell metabolism to exert their anticancer activities remains unknown. In this study, we explore the metabolic features characterising MYC-driven MB and examine how these are altered by BET-bromodomain inhibition. To this end, we employed an NMR-based metabolomics approach applied to the MYC-driven MB D283 and D458 cell lines before and after the treatment with the BETi OTX-015. We found that OTX-015 triggers a metabolic shift in both cell lines resulting in increased levels of myo-inositol, glycerophosphocholine, UDP-N-acetylglucosamine, glycine, serine, pantothenate and phosphocholine. Moreover, we show that OTX-015 alters ascorbate and aldarate metabolism, inositol phosphate metabolism, phosphatidylinositol signalling system, glycerophospholipid metabolism, ether lipid metabolism, aminoacyl-tRNA biosynthesis, and glycine, serine and threonine metabolism pathways in both cell lines. These insights provide a metabolic characterisation of MYC-driven childhood MB cell lines, which could pave the way for the discovery of novel druggable pathways. Importantly, these findings will also contribute to understand the downstream effects of BETis on MYC-driven MB, potentially aiding the development of new therapeutic strategies to combat medulloblastoma.

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Section: Discussionmentioning

confidence: 99%

Metabolic rewiring in MYC-driven medulloblastoma by BET-bromodomain inhibition

Graziani

Garcia

Alcolado

et al. 2023

Sci Rep

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“…It has been shown that polysaccharides modulated the immune system by regulating immune cells [ 23 ]. Macrophage activation played an important role in immunological activity, and this activation secretes cytokines such as TNF-α, interleukin-1 (IL-1), IL-6, and interferon (IFN)-α/β participated in the regulation of cellular defense [ 24 ]. TNF-α is a representative cytokine that supports the immune system and induces inflammation.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Activity and Its Mechanisms of Two Polysaccharides from Poria cocos

Zhang,

He,

Zheng

et al. 2023

Molecules

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Polyporaceae is an important fungal family that has been a source of natural products with a range of pharmaceutical activities in China. In our previous study, two polysaccharides, PCWPW and PCWPS, with significant antioxidant and antidepressant activity were obtained from Poria cocos. In this study, we evaluated their potential molecular mechanisms in the immunomodulation of macrophages. PCWPW and PCWPS were characterized by GC–MS analysis to contain 1,3-linked Glcp. ELISA assays results demonstrated that the secretion of TNF-α was significantly enhanced by PCWPW/PCWPS. RNA-seq data demonstrated that PCWPS treatment modulated the expression of immune-related genes in macrophages, which was further confirmed by RT-qPCR assays. The activation of TNF-α secretion was found to be mannose receptor (MR) dependent and suppressed by MR inhibitor pretreatment. Moreover, the amount of TNF-α cytokine secretion in PCWPW/PCWPS-induced RAW264.7 cells was decreased when pretreated with NF-κB or MAPK signaling pathway inhibitors. Collectively, our results suggested that PCWPW and PCWPS possessed immunomodulatory activity that regulates TNF-α expression through the NF-κB/MAPK signaling pathway by binding to mannose receptors. Therefore, PCWPW and PCWPS isolated from Poria cocos have potential as drug candidates for immune-related disease treatment.

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“…Since it was discovered twenty years ago, TNF has been known as an anti-cancer agent while also having a multifunctional impact on lipid metabolism, coagulation, insulin resistance, and endothelial function [49]. Cells can receive both survival and death signals from members of the TNFR superfamily [50]. Tumor necrosis factor alpha (TNF-α) is a versatile cytokine that plays a crucial role in regulating numerous signaling pathways associated with inflammation, immunity, apoptosis (cell death), anti-apoptosis (cell survival), and even the development of tumors [51].…”

Section: Enrichment Analysis Of Go and Kegg Pathways On The Basis Of ...mentioning

confidence: 99%

Transcriptome Analysis Revealed Potential Immune-Related Genes of Head Kidney in the Yellow Catfish (Pelteobagrus fulvidraco) Challenged with Aeromonas hydrophila

Jiang,

Lei,

Wang

et al. 2024

Fishes

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Yellow catfish (Pelteobagrus fulvidraco) is an important freshwater fish species in aquaculture. However, as intensive farming has rapidly expanded, infectious diseases caused by various bacteria, such as Aeromonas hydrophila, have also increased. We conducted a transcriptomic analysis of head kidney from P. fulvidraco stimulated by A. hydrophila strain SHOU. A total of 43,249 unigenes with an average length of 1342 bp were obtained following assembly and annotation. By analyzing GO and KEGG enrichment, many differentially expressed genes (DEGs) and pathways related to immunity were identified. Out of the 973 DEGs that were identified, 553 were upregulated and 420 were downregulated. Moreover, KEGG enrichment analysis revealed that the innate immune system, including the TNF signaling pathway, NF-kappa B signaling pathway, and the Toll-like receptor signaling pathway involved in the defense, is activated against infectious response. Real-time quantitative reverse transcription-PCR (qRT-PCR) analysis demonstrated that immune response genes were upregulated in response to A. hydrophila stimulation compared to the control. In conclusion, this study provides valuable insights into the immune defense mechanism of P. fulvidraco and sheds light on the host immune genes involved in the response to bacterial infection.

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Development of a prognostic model based on an immunogenomic landscape analysis of medulloblastoma

Cited by 5 publications

References 71 publications

Metabolic rewiring in MYC-driven medulloblastoma by BET-bromodomain inhibition

Metabolic rewiring in MYC-driven medulloblastoma by BET-bromodomain inhibition

Immunomodulatory Activity and Its Mechanisms of Two Polysaccharides from Poria cocos

Transcriptome Analysis Revealed Potential Immune-Related Genes of Head Kidney in the Yellow Catfish (Pelteobagrus fulvidraco) Challenged with Aeromonas hydrophila

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