CircGLIS3 promotes high-grade glioma invasion via modulating Ezrin phosphorylation (microarray)
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ABSTRACT:
PROVIDER: PRJNA698582 | ENA |
REPOSITORIES: ENA
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Project description:High-grade glioma is highly aggressive and malignant, resistant to combined therapies and easy to relapse. A better understanding of circRNA biological function in high-grade glioma might contribute to the therapeutic efficacy. Here, a circRNA merely up-regulated in high-grade glioma, circGLIS3 (hsa_circ_0002874, originating from exon 2 of GLIS3), was validated by microarray and qRT-PCR. Functional experiments uncovered that up-regulation of circGLIS3 promoted glioma cell migration and invasion, and showed aggressive characteristics in tumor-bearing mice. Fluorescence in situ hybridization, RNA pull-down, RNA immunoprecipitation and immunohistochemical staining showed that circGLIS3 could promoted Ezrin T567 phosphorylation. Further investigation showed that circGLIS3 could be excreted by glioma through exosomes and induced endothelial cells angiogenesis. This study indicates that circGLIS3 is up-regulated in high-grade glioma and contributes to the invasion and angiogenesis of glioma via promoting Ezrin T567 phosphorylation.
2021-09-22 | GSE165859 | GEO
Project description:High-grade glioma is highly aggressive and malignant, resistant to combined therapies and easy to relapse. A better understanding of circRNA biological function in high-grade glioma might contribute to the therapeutic efficacy. Here, a circRNA merely up-regulated in high-grade glioma, circGLIS3 (hsa_circ_0002874, originating from exon 2 of GLIS3), was validated by microarray and qRT-PCR. Functional experiments uncovered that up-regulation of circGLIS3 promoted glioma cell migration and invasion, and showed aggressive characteristics in tumor-bearing mice. Fluorescence in situ hybridization, RNA pull-down, RNA immunoprecipitation and immunohistochemical staining showed that circGLIS3 could promoted Ezrin T567 phosphorylation. Further investigation showed that circGLIS3 could be excreted by glioma through exosomes and induced endothelial cells angiogenesis. This study indicates that circGLIS3 is up-regulated in high-grade glioma and contributes to the invasion and angiogenesis of glioma via promoting Ezrin T567 phosphorylation.
2021-09-22 | GSE165926 | GEO
Project description:CircGLIS3 promotes high-grade glioma invasion via modulating Ezrin phosphorylation
| PRJNA698359 | ENA
Project description:High-grade glioma is highly invasive and malignant, resistant to combined therapies, and easy to relapse. A better understanding of circular RNA (circRNA) biological function in high-grade glioma might contribute to the therapeutic efficacy. Here, a circRNA merely upregulated in high-grade glioma, circGLIS3 (hsa_circ_0002874, originating from exon 2 of GLIS3), was validated by microarray and Real-time quantitative reverse transcription PCR (qRT-PCR). The role of circGLIS3 in glioma was assessed by functional experiments both in vitro and in vivo. Fluorescence in situ hybridization (FISH), RNA pull-down, RNA immunoprecipitation (RIP), and immunohistochemical staining were performed for mechanistic study. Cocultured brain endothelial cells with glioma explored the role of exosome-derived circGLIS3 in the glioma microenvironment. We found that upregulation of circGLIS3 promoted glioma cell migration and invasion and showed aggressive characteristics in tumor-bearing mice. Mechanistically, we found that circGLIS3 could promote the Ezrin T567 phosphorylation level. Moreover, circGLIS3 could be excreted by glioma through exosomes and induced endothelial cell angiogenesis. Our findings indicate that circGLIS3 is upregulated in high-grade glioma and contributes to the invasion and angiogenesis of glioma via modulating Ezrin T567 phosphorylation.
| S-EPMC8446459 | biostudies-literature
Project description:It has been shown that up regulation activity of CD81(TAPA-1, the portal of entry of Hepatitis C virus) by agonistic antibody results in phosphorylation of Ezrin. We have previously shown that in liver, Ezrin phosphorylation occurs via Syk kinase, causing suppression of hippo intensity, therefore increases sequential Yap activity. The opposite occurs when Glypican-3 (GPC3) or E2 protein of HCV bind to CD81. Mice over-expressing GPC3 in hepatocytes have decreased p-Ezrin(Thr567) and Yap, increased Hippo activity and suppressed liver regeneration. The role of Ezrin in these processes has been speculated, but not proven. We now provide dynamic picture of Ezrin regulates Hippo pathway and Yap. Forced expression of plasmids expressing mutant Ezrin (T567D) (which mimics p-Ezrin(Thr567)) suppressed Hippo activity and activated Yap signaling. And this mutant Ezrin drive more cell proliferation to cell division through up regulated Yap activity in vitro and in vivo. CD81 loses expression, while p-Ezrin(Thr567) increases in JM1 and JM2 hepatocellular carcinoma (HCC) cells. Administration with compound NSC668394, a characterized p-Ezrin(Thr567) antagonist, caused significant decrease in HCC cell proliferation. We additionally present evidence that pEzrin(T567) is also controlled by EGFR and MET. Conclusions: Ezrin phosphorylation, mediated by CD81 associated Syk kinase, is directly involved in regulation of Hippo pathway, Yap levels and growth rates of normal and neoplastic hepatocytes. The finding has mechanistic and potentially therapeutic applications in understanding and regulating growth of hepatocytes and HCC and HCV pathogenesis. We used microarrays to detail the global programme of gene expression in GFP positive hepatocytes of FVB mice adminstration with EzrinT567D plasmids
2020-03-27 | GSE145572 | GEO
Project description:Analysis of SW480 cells following knockdown of Ezrin using RNAi. Ezrin is a protein that regulate the organization of cytoskeleton. Ezrin KD SW480 was used to study the role of ezrin in colon cancer. Keywords: ezrin, colon cancer, migration
2008-04-29 | GSE11279 | GEO
Project description:Oxidative phosphorylation promotes primary melanoma invasion
| PRJNA602818 | ENA
Project description:Analysis of SW480 cells following knockdown of Ezrin using RNAi. Ezrin is a protein that regulate the organization of cytoskeleton. Ezrin KD SW480 was used to study the role of ezrin in colon cancer. Experiment Overall Design: Knockdown ezrin in SW480 cells and investigate the affection on cell migration and the downstream genes.
2008-06-11 | E-GEOD-11279 | biostudies-arrayexpress
Project description:Ezrin (EZR), a cell membrane to cytoskeleton linker protein, plays key roles in maintaining cellular homeostasis. Its deregulation at various levels strongly correlates with cancer progression, metastasis and higher patient mortality. However, the precise mechanistic basis for its role remains unknown. Recently, we demonstrated that Ezrin participates in EGFR/AKT signaling pathways. Importantly, transitions between active (phosphorylated open) and inactive (dephosphorylated closed) forms of Ezrin is crucial for its function in cancer. Gene expression analysis suggested dysregulation of genes that are functionally linked to cell energetic metabolism with potential implications for cell proliferation, survival and apoptosis. Total RNA was extracted from n=4 for each experimantal group: Transcriptomic analysis was performed on HeLa WT and HeLa Ezrin KO cells.
2025-09-30 | GSE288769 | GEO
Project description:Ezrin (EZR), a cell membrane to cytoskeleton linker protein, plays key roles in maintaining cellular homeostasis. Its deregulation at various levels strongly correlates with cancer progression, metastasis and higher patient mortality. However, the precise mechanistic basis for its role remains unknown. Recently, we demonstrated that Ezrin participates in EGFR/AKT signaling pathways. Importantly, transitions between active (phosphorylated open) and inactive (dephosphorylated closed) forms of Ezrin is crucial for its function in cancer. Gene expression analysis suggested dysregulation of genes that are functionally linked to cell energetic metabolism with potential implications for cell proliferation, survival and apoptosis. Total RNA was extracted from n=4 for each experimantal group: Transcriptomic analysis was performed on HeLa DMSO and Ezrin inhibitor-treated cells.
2025-09-30 | GSE288768 | GEO