The Role of N-myc Downstream-Regulated Gene Family in Glioma Based on Bioinformatics Analysis

Tang, Ting; Wang, Handong; Han, Yanling; Huang, Han-Yu; Niu, Wenhao; Fei, Maoxing; Zhu, Yihao

doi:10.1089/dna.2020.6216

Cited by 2 publications

(1 citation statement)

References 66 publications

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“…Therefore, PP2A-activating compounds may be effective in cancers with functional NDRG2 and may synergize with PRMT5 inhibiting compounds, while NDRG2 deletions may render this strategy ineffective. Conversely, in glioblastoma, PRMT5 exhibits a tumor suppressive role, while NDRG2 is reported to have oncogenic properties ( 122 , 123 ). Consistent with the findings, treatment of glioblastoma with PP2A-inhibitor LB100 has an anti-tumor effect in the context of PRMT5 regulation ( 122 ).…”

Section: Interplay Of Pp2a and Chromatin Remodeling Complexesmentioning

confidence: 99%

PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen

Tinsley

Allen-Petersen

2022

NAR Cancer

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The epigenetic state of chromatin is altered by regulators which influence gene expression in response to environmental stimuli. While several post-translational modifications contribute to chromatin accessibility and transcriptional programs, our understanding of the role that specific phosphorylation sites play is limited. In cancer, kinases and phosphatases are commonly deregulated resulting in increased oncogenic signaling and loss of epigenetic regulation. Aberrant epigenetic states are known to promote cellular plasticity and the development of therapeutic resistance in many cancer types, highlighting the importance of these mechanisms to cancer cell phenotypes. Protein Phosphatase 2A (PP2A) is a heterotrimeric holoenzyme that targets a diverse array of cellular proteins. The composition of the PP2A complex influences its cellular targets and activity. For this reason, PP2A can be tumor suppressive or oncogenic depending on cellular context. Understanding the nuances of PP2A regulation and its effect on epigenetic alterations can lead to new therapeutic avenues that afford more specificity and contribute to the growth of personalized medicine in the oncology field. In this review, we summarize the known PP2A-regulated substrates and potential phosphorylation sites that contribute to cancer cell epigenetics and possible strategies to therapeutically leverage this phosphatase to suppress tumor growth.

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Section: Interplay Of Pp2a and Chromatin Remodeling Complexesmentioning

confidence: 99%

PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen

Tinsley

Allen-Petersen

2022

NAR Cancer

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Aloperine targets lysosomes to inhibit late autophagy and induces cell death through apoptosis and paraptosis in glioblastoma

Tang,

Liang,

Wei

et al. 2023

Mol Biomed

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Glioblastoma (GBM) is an aggressive intracranial tumour, and current chemotherapy regimens have limited efficacy. Aloperine (ALO), a natural alkaline compound, has shown potential as an antitumor agent. However, the effect of ALO against GBM remains unclear. This study aimed to investigate the function of ALO in treating GBM. U87, A172, and GL261 cell lines were used for in vitro experiments, and GL261 was also used to establish in vivo models. The results showed that ALO inhibited the proliferation of GBM cells by cell cycle arrest and apoptosis. Furthermore, autophagy was found to play a critical role, suggested by observation of autophagosomes under the transmission electron microscopy. It was discovered for the first time that ALO targeted lysosomes directly in glioma cells, tested by fluo-rescence-labelled ALO and organelle-localizing probes. In addition, ALO inhibited late autophagy and induced paraptosis in GBM, verified by classical gene expression changes in qPCR and western blotting. Also, ALO inhibited tumour growth and acted synergistically with temozolomide in intracranial glioma mice models in vivo. Our findings suggest that ALO targets lysosomes to inhibit late autophagy in GBM, inducing cell cycle arrest, paraptosis, and apoptosis. ALO may therefore be a promising therapeutic agent for the treatment of GBM.

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The Role of N-myc Downstream-Regulated Gene Family in Glioma Based on Bioinformatics Analysis

Cited by 2 publications

References 66 publications

PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen

PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen

Aloperine targets lysosomes to inhibit late autophagy and induces cell death through apoptosis and paraptosis in glioblastoma

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