EZH2-Inhibited MicroRNA-454-3p Promotes M2 Macrophage Polarization in Glioma

Qi, Bin; Yang, Cheng Chieh; Zhu, Zhanpeng; Chen, Hao

doi:10.3389/fcell.2020.574940

Cited by 22 publications

(18 citation statements)

References 39 publications

(37 reference statements)

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“…There is a fact that up to 30–50% of the immune cells in glioma are tumor-associated macrophages (TAMs). 38 Previous investigators have classified TAMs into M1-type macrophages, a proinflammatory phenotype associated with a favorable survival outcome, and M2-type macrophages, an immunosuppressive phenotype associated with a poor survival outcome. 39 Our results suggested that M2-type macrophages had an overwhelming advantage in numbers compared with other immune cells, and the PRGPI-high group with poor survival outcome had significantly higher enrichment of M2-type macrophages.…”

Section: Discussionmentioning

confidence: 99%

A Pyroptosis-Related Gene Prognostic Index Correlated with Survival and Immune Microenvironment in Glioma

Zheng¹,

Zhou²,

Qiu³

et al. 2022

JIR

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As an inflammatory form of programmed cell death, pyroptosis has been well established to be associated with tumorigenesis and tumor immune microenvironment. In this paper, we aimed at the construction of a pyroptosis-related gene prognostic index (PRGPI) for predicting prognosis and guiding individualized immunotherapy in glioma patients. Patients and Methods: Pyroptosis-related genes (PRGs) were identified based on a detailed review of published literatures. The transcriptome data and clinical information of glioma patients were obtained from CGGA and TCGA databases. PRGPI was constructed by using the multivariate Cox regression method. The immune cell infiltration level was analyzed via CIBERSORT algorithm. The tumor immune dysfunction and exclusion (TIDE) algorithm was applied to evaluate the potential response to immune checkpoint inhibitor (ICI) therapy. The expression patterns of PRGs in PRGPI were validated in cell lines and pathological specimens. Results: We identified a total of 31 PRGs. Among them, PRGs (CASP3, DPP9, MAPK8, PELP1 and TOMM20) were selected for the construction of PRGPI. In both training (CGGA693) and validation (CGGA325 and TCGA) cohorts, PRGPI-high patients showed an inferior survival outcome compared with PRGPI-low patients. ROC curves illustrated that the prognostic prediction power of PRGPI was robust. A nomogram was developed based on independent prognostic indicators (PRGPI, age and WHO grade), and also exhibited a strong forecasting ability for overall survival (OS). Additionally, PRGPI-high patients exhibited higher immune, stroma and ESTIMATE scores, lower tumor purity, higher infiltration of M2type macrophages, lower infiltration of CD8 + T cells and activated NK cells, higher tumor mutation burden (TMB), and higher expression of immune checkpoints. TIDE showed that PRGPI-high group had more responders of ICI therapy than PRGPI-low group. Finally, the expression patterns of five selected PRGs in PRGPI were significantly different between normal and glioma. Conclusion:The constructed PRGPI can be used for predicting prognosis and guiding individualized immunotherapy in glioma patients.

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Section: Discussionmentioning

confidence: 99%

A Pyroptosis-Related Gene Prognostic Index Correlated with Survival and Immune Microenvironment in Glioma

Zheng¹,

Zhou²,

Qiu³

et al. 2022

JIR

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“…Furthermore, the histone methyltransferase EZH2 utilizes a methylation modification to inhibit miR-454-3p and promotes the m6A modification of PTEN to polarize macrophages toward the M2 phenotype. Of note, combined treatment with EZH2 inhibitors and PD-1 inhibitors restored the cytotoxicity of macrophages and blocked the progression of CSCs [ 205 , 206 , 207 , 208 , 209 , 210 , 211 , 212 ].…”

Section: Therapeutic Strategies Targeting Cscs and Tamsmentioning

confidence: 99%

Macrophages Are a Double-Edged Sword: Molecular Crosstalk between Tumor-Associated Macrophages and Cancer Stem Cells

Luo

Yang

et al. 2022

Biomolecules

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Cancer stem cells (CSCs) are a subset of highly tumorigenic cells in tumors. They have enhanced self-renewal properties, are usually chemo-radioresistant, and can promote tumor recurrence and metastasis. They can recruit macrophages into the tumor microenvironment and differentiate them into tumor-associated macrophages (TAMs). TAMs maintain CSC stemness and construct niches that are favorable for CSC survival. However, how CSCs and TAMs interact is not completely understood. An understanding on these mechanisms can provide additional targeting strategies for eliminating CSCs. In this review, we comprehensively summarize the reported mechanisms of crosstalk between CSCs and TAMs and update the related signaling pathways involved in tumor progression. In addition, we discuss potential therapies targeting CSC–TAM interaction, including targeting macrophage recruitment and polarization by CSCs and inhibiting the TAM-induced promotion of CSC stemness. This review also provides the perspective on the major challenge for developing potential therapeutic strategies to overcome CSC-TAM crosstalk.

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“…For example, in hepatocellular carcinoma, miR-144/miR-451a is silenced by EZH2 and promotes M1 polarization, enhancing anti-tumor immunity [ 221 ]. In addition, EZH2 is inhibited in gliomas, mediated in a PRC2-dependent manner through miRNA-454-3p, immunosuppression or M2-like macrophage polarization [ 222 ]. However, macrophage infiltration is involved in the regulation of the LOX family protein (LOXL4) by EZH2-miR-29b/miR-30d in invasive breast cancer, and contributes to extracellular matrix remodeling [ 223 ].…”

Section: Immune Regulation By Ezh2 In Tmementioning

confidence: 99%

Polycomb Directed Cell Fate Decisions in Development and Cancer

Germán

Ellis

2022

Epigenomes

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The polycomb group (PcG) proteins are a subset of transcription regulators highly conserved throughout evolution. Their principal role is to epigenetically modify chromatin landscapes and control the expression of master transcriptional programs to determine cellular identity. The two mayor PcG protein complexes that have been identified in mammals to date are Polycomb Repressive Complex 1 (PRC1) and 2 (PRC2). These protein complexes selectively repress gene expression via the induction of covalent post-translational histone modifications, promoting chromatin structure stabilization. PRC2 catalyzes the histone H3 methylation at lysine 27 (H3K27me1/2/3), inducing heterochromatin structures. This activity is controlled by the formation of a multi-subunit complex, which includes enhancer of zeste (EZH2), embryonic ectoderm development protein (EED), and suppressor of zeste 12 (SUZ12). This review will summarize the latest insights into how PRC2 in mammalian cells regulates transcription to orchestrate the temporal and tissue-specific expression of genes to determine cell identity and cell-fate decisions. We will specifically describe how PRC2 dysregulation in different cell types can promote phenotypic plasticity and/or non-mutational epigenetic reprogramming, inducing the development of highly aggressive epithelial neuroendocrine carcinomas, including prostate, small cell lung, and Merkel cell cancer. With this, EZH2 has emerged as an important actionable therapeutic target in such cancers.

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EZH2-Inhibited MicroRNA-454-3p Promotes M2 Macrophage Polarization in Glioma

Cited by 22 publications

References 39 publications

A Pyroptosis-Related Gene Prognostic Index Correlated with Survival and Immune Microenvironment in Glioma

A Pyroptosis-Related Gene Prognostic Index Correlated with Survival and Immune Microenvironment in Glioma

Macrophages Are a Double-Edged Sword: Molecular Crosstalk between Tumor-Associated Macrophages and Cancer Stem Cells

Polycomb Directed Cell Fate Decisions in Development and Cancer

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