Disruption of β-catenin-mediated negative feedback reinforces cAMP-induced neuronal differentiation in glioma stem cells

Chen, Zhijie; Zhong, Yingqian; Chen, Jiehong; Sun, Shuxin; Liu, Wenfeng; Han, Yu; Liu, Xincheng; Guo, Cui; Li, De-Pei; Hu, Wanming; Zhang, Peiyu; Chen, Zhuopeng; Chen, Zhongping; Mou, Yonggao; Gao, Yan; Zhu, Wenbo; Yin, Wei; Sai, Ke

doi:10.1038/s41419-022-04957-9

Cited by 10 publications

(9 citation statements)

References 59 publications

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“…To clarify if CM combination has the same differentiation-inducing effect on glioma stem cells (GSCs) which are recurrence seeds of glioma, we evaluated the phenotype change, the transcriptome profile, and the profile of genes marked by H3K9ac and H3K14ac. First, we used two GSCs lines GSC1 and GSC11, both of which have been systematically validated to be characterized with stem cell properties [ 17 – 20 ]. Consistent with data from U87MG cells, CM-treated GSC cells were characterized by shrinking cell bodies and long synapse-like structure (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…GSC1 and GSC11 cell lines were derived from human GBM tumor samples and were characterized as reported previously [ 17 – 20 ]. Briefly, freshly resected GBM tissues were cut into small pieces, washed three times in DMEM/F12 medium (Gibco, Carlsbad, CA, USA), digested with trypsin (Gibco), triturated mechanically with surgical scissors, and filtered through a cell strainer (BD Biosciences, Franklin Lakes, NJ, USA).…”

Section: Methodsmentioning

confidence: 99%

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Differential regulation of H3K9/H3K14 acetylation by small molecules drives neuron-fate-induction of glioma cell

et al. 2023

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Differentiation therapy using small molecules is a promising strategy for improving the prognosis of glioblastoma (GBM). Histone acetylation plays an important role in cell fate determination. Nevertheless, whether histone acetylation in specific sites determines GBM cells fate remains to be explored. Through screening from a 349 small molecule-library, we identified that histone deacetylase inhibitor (HDACi) MS-275 synergized with 8-CPT-cAMP was able to transdifferentiate U87MG GBM cells into neuron-like cells, which were characterized by cell cycle arrest, rich neuron biomarkers, and typical neuron electrophysiology. Intriguingly, acetylation tags of histone 3 at lysine 9 (H3K9ac) were decreased in the promoter of multiple oncogenes and cell cycle genes, while ones of H3K9ac and histone 3 at lysine 14 (H3K14ac) were increased in the promoter of neuron-specific genes. We then compiled a list of genes controlled by H3K9ac and H3K14ac, and proved that it is a good predictive power for pathologic grading and survival prediction. Moreover, cAMP agonist combined with HDACi also induced glioma stem cells (GSCs) to differentiate into neuron-like cells through the regulation of H3K9ac/K14ac, indicating that combined induction has the potential for recurrence-preventive application. Furthermore, the combination of cAMP activator plus HDACi significantly repressed the tumor growth in a subcutaneous GSC-derived tumor model, and temozolomide cooperated with the differentiation-inducing combination to prolong the survival in an orthotopic GSC-derived tumor model. These findings highlight epigenetic reprogramming through H3K9ac and H3K14ac as a novel approach for driving neuron-fate-induction of GBM cells.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Differential regulation of H3K9/H3K14 acetylation by small molecules drives neuron-fate-induction of glioma cell

et al. 2023

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“…The caspase recruitment domain (CARD) regulates signaling pathways related to innate immune responses, caspase activation, and inflammasome assembly. [ 25 ] CARD16 (also known as pseudo-ICE) comprises 97 amino acids containing a solitary CARD motif. [ 25 26 ] CARD16 can bind with the CARD of caspase-1 (CASP1) and negatively regulate CASP1 activity.…”

Section: Discussionmentioning

confidence: 99%

“…[ 25 ] CARD16 (also known as pseudo-ICE) comprises 97 amino acids containing a solitary CARD motif. [ 25 26 ] CARD16 can bind with the CARD of caspase-1 (CASP1) and negatively regulate CASP1 activity. [ 27 ] According to the literature, the loss of CASP1 can decrease the transcription levels of inflammatory factors and reduce the recruitment of pulmonary neutrophils.…”

Section: Discussionmentioning

confidence: 99%

Explore the role of long noncoding RNAs and mRNAs in intracranial atherosclerotic stenosis: From the perspective of neutrophils

Wang,

Han

et al. 2023

Brain Circulation

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CONTEXT: Circulating neutrophils and long noncoding RNAs (lncRNAs) play various roles in intracranial atherosclerotic stenosis (ICAS). OBJECTIVE: Our study aimed to detect differentially expressed (DE) lncRNAs and mRNAs in circulating neutrophils and explore the pathogenesis of atherosclerosis from the perspective of neutrophils. METHODS: Nineteen patients with ICAS and 15 healthy controls were enrolled. The peripheral blood of the participants was collected, and neutrophils were separated. The expression profiles of lncRNAs and mRNAs in neutrophils from five patients and five healthy controls were obtained, and DE lncRNAs and mRNAs were selected. Six lncRNAs were selected and validated using quantitative reverse transcription–polymerase chain reaction (qRT-PCR), and ceRNA and lncRNA-RNA binding protein (RBP)-mRNA networks were constructed. Correlation analysis between lncRNAs and mRNAs was performed. Functional enrichment annotations were also performed. RESULTS: Volcano plots and heat maps displayed the expression profiles and DE lncRNAs and mRNAs, respectively. The qRT-PCR results revealed that the four lncRNAs showed a tendency consistent with the expression profile, with statistical significance. The ceRNA network revealed three pairs of regulatory networks: lncRNA RP3-406A7.3-NAGLU, lncRNA HOTAIRM1-MVK/IL-25/GBF1/CNOT4/ANKK1/PLEKHG6, and lncRNA RP11-701H16.4-ZNF416. The lncRNA-RBP-mRNA network showed five pairs of regulatory networks: lncRNA RP11-701H16.4-TEK, lncRNA RP11-701H16.4-MED17, lncRNA SNHG19-NADH-ubiquinone oxidoreductase core subunit V1, lncRNA RP3-406A7.3-Angel1, and lncRNA HOTAIRM1-CARD16. CONCLUSIONS: Our study identified and verified four lncRNAs in neutrophils derived from peripheral blood, which may explain the transcriptional alteration of neutrophils during the pathophysiological process of ICAS. Our results provide insights for research related to the pathogenic mechanisms and drug design of ICAS.

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“…Helena C found that GSCs-derived cells didn't undergo terminal cell cycle arrest and remain vulnerable to de-differentiation. When differentiation stimulation being withdrawn, they may return to GSC-like cells with proliferative potential (34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

Global research trends and hotspots on glioma stem cells

Song

Wu²,

Wang³

et al. 2022

Front. Oncol.

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BackgroundGlioma stem cells (GSCs) are a sub-population of cancer stem cells with capacity of self-renewal and differentiation. Accumulated evidence has revealed that GSCs were shown to contribute to gliomagenesis, distant metastasis as well as the resistance to radiotherapy and chemotherapy. As a result, GSCs were regarded as a promising therapeutic target in human glioma. The purpose of our study is to identify current state and hotspots of GSCs research by analyzing scientific publications through bibliometric methods.MethodsAll relevant publications on GSCs during 2003-2021 were extracted from the Science Citation Index Expanded of Web of Science Core Collection (WoSCC), and related information was collected and analyzed using Microsoft Excel 2016, GraphPad Prism 8 and VOSviewer software.ResultsA total of 4990 papers were included. The United States accounted for the largest number of publications (1852), the second average citations per item (ACI) value (67.54) as well as the highest H-index (157). Cancer Research was the most influential journal in this field. The most contributive institution was League of European Research Universities. RICH JN was the author with the most publications (109) and the highest H-index (59). All studies were clustered into 3 groups: “glioma stem cell properties”, “cell biological properties” and “oncology therapy”. The keywords “identification”, “CD133” and “side population” appeared earlier with the smaller average appearing years (AAY), and the keywords”radiotherapy” and “chemotherapy” had the latest AAY. The analysis of top cited articles showed that “temozolomide”, “epithelial-mesenchymal transition”, and “immunotherapy” emerged as new focused issues.ConclusionThere has been a growing number of researches on GSCs. The United States has always been a leading player in this domain. In general, the research focus has gradually shifted from basic cellular biology to the solutions of clinical concerns. “Temozolomide resistance”, “epithelial-mesenchymal transition”, and “immunotherapy” should be given more attention in the future.

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Disruption of β-catenin-mediated negative feedback reinforces cAMP-induced neuronal differentiation in glioma stem cells

Cited by 10 publications

References 59 publications

Differential regulation of H3K9/H3K14 acetylation by small molecules drives neuron-fate-induction of glioma cell

Differential regulation of H3K9/H3K14 acetylation by small molecules drives neuron-fate-induction of glioma cell

Explore the role of long noncoding RNAs and mRNAs in intracranial atherosclerotic stenosis: From the perspective of neutrophils

Global research trends and hotspots on glioma stem cells

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