PRMT5 promotes cancer cell migration and invasion through the E2F pathway
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ABSTRACT:
PROVIDER: PRJNA597013 | ENA |
REPOSITORIES: ENA
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Project description:We identified distinct sets of genes under the control of PRMT5 and E2F1. Some of the most highly regulated genes, such as cortactin/CTTN, influenced cell migration, invasion and adherence. We characterised the functional role of the cortactin/CTTN gene, which enabled PRMT5 through E2F1 to promote cellular migration and invasion, whilst decreasing cellular adherence. Most significantly, there was a striking coincidence between the expression of PRMT5 and E2F1 in certain human tumours, and elevated levels of PRMT5, E2F1 and cortactin/CTTN correlated with poor prognosis disease. Our results suggest a causal relationship between PRMT5, E2F1 and the migration and invasion of cancer cells, thereby highlighting an important pathway that contributes to the cancer biology of tumour cells.
2020-07-28 | GSE142430 | GEO
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Project description:E2F activity impacts on an extensive gene network mediated in part by PRMT5-dependent arginine methylation which widens its functional role in gene expression control. We show here that the PRMT5-E2F1 axis has an additional and unexpected level of control through facilitating expression of the non-coding genome where long non-coding (lnc) genes are direct targets for PRMT5 and E2F1. The expression of some lncRNAs results in their translation into small proteins, which then give rise to peptides which populate the MHC class I antigen presentation machinery. Pharmacological inhibition of PRMT5 alters the expression of lncRNA genes and thereby the repertoire lncRNA-derived peptides presented as MHC bound peptides. Delayed tumor growth upon PRMT5 inhibition reflects an influx of lncRNA peptide-specific cytotoxic CD8 T cells. When presented to the immune system as a stand-alone therapeutic vaccine, lncRNA-derived MHC-bound peptides are immunogenic and drive a potent anti-tumor T cell response with a significant delay in tumor growth. Our results show that the PRMT5 through its control of the E2F pathway influences expression of the non-coding genome and derived peptides presented to the immune system, which can subsequently be harnessed to deliver an effective stand-alone cancer vaccine. These results have important implications for deploying pharmacological intervention to manipulate gene expression and antigen presentation to the immune system and deploying new types of cancer vaccine. They also indicate that cell cycle control through the E2F pathway is intimately connected with immune recognition.
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Project description:Immunopeptidomics analyses of CT26 cells +/- PRMT5 inhibition
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Project description:Protein arginine methyltransferase 5 (Prmt5) is the major type II methyltransferase catalyzing symmetric dimethylation, regulates cell development, homeostatic and disease processes. Prmt5 inhibition or deletion in CD4+T cells has been reported to protection against experimental autoimmune encephalomyelitis (EAE), the perfect mouse model for multiple sclerosis (MS); however, the detail mechanisms have not yet been elucidated. Here, using the mRNA sequencing, single cell RNA sequencing and ATAC sequencing, we uncovered the unreported role of Prmt5 on T cells migration ability under the EAE condition. We found that mice condition knockout of Prmt5 in T cells were resistance with EAE, infiltrating inflammatory CD4+ T cells in center nervous system (CNS) were greatly reduced. However, T cells in spleen showed much more proliferation and activation properties in Prmt5cko mice, the number of pathogenic CD4+T cells in spleen were not reduced. We further revealed that Rora+CD4+T cells were elevated in Prmt5cko mice, but expressed lower level of S1pr1, resulting in a lack of CD4+ T cells egress from spleen and migrate to CNS, leading to pathogenic CD4+T cells were blocked in spleen. Moreover, single cell ATAC sequencing revealed that Klf2 were enriched in S1pr1 promoter and reduced in Prmt5cko mice. Correctively, our study delineated the undiscovered role of Prmt5 on T cell biology, Prmt5 may through Klf2-S1pr1 pathway and regulate T cells migration; modulating Prmt5 levels may be useful for controlling CD4+T cell migration in CD4+T cell mediated diseases including MS.
2023-08-09 | GSE195887 | GEO
Project description:Protein arginine methyltransferase 5 (Prmt5) is the major type II methyltransferase catalyzing symmetric dimethylation, regulates cell development, homeostatic and disease processes. Prmt5 inhibition or deletion in CD4+T cells has been reported to protection against experimental autoimmune encephalomyelitis (EAE), the perfect mouse model for multiple sclerosis (MS); however, the detail mechanisms have not yet been elucidated. Here, using the mRNA sequencing, single cell RNA sequencing and ATAC sequencing, we uncovered the unreported role of Prmt5 on T cells migration ability under the EAE condition. We found that mice condition knockout of Prmt5 in T cells were resistance with EAE, infiltrating inflammatory CD4+ T cells in center nervous system (CNS) were greatly reduced. However, T cells in spleen showed much more proliferation and activation properties in Prmt5cko mice, the number of pathogenic CD4+T cells in spleen were not reduced. We further revealed that Rora+CD4+T cells were elevated in Prmt5cko mice, but expressed lower level of S1pr1, resulting in a lack of CD4+ T cells egress from spleen and migrate to CNS, leading to pathogenic CD4+T cells were blocked in spleen. Moreover, single cell ATAC sequencing revealed that Klf2 were enriched in S1pr1 promoter and reduced in Prmt5cko mice. Correctively, our study delineated the undiscovered role of Prmt5 on T cell biology, Prmt5 may through Klf2-S1pr1 pathway and regulate T cells migration; modulating Prmt5 levels may be useful for controlling CD4+T cell migration in CD4+T cell mediated diseases including MS.
2023-08-09 | GSE195882 | GEO
Project description:Protein arginine methyltransferase 5 (Prmt5) is the major type II methyltransferase catalyzing symmetric dimethylation, regulates cell development, homeostatic and disease processes. Prmt5 inhibition or deletion in CD4+T cells has been reported to protection against experimental autoimmune encephalomyelitis (EAE), the perfect mouse model for multiple sclerosis (MS); however, the detail mechanisms have not yet been elucidated. Here, using the mRNA sequencing, single cell RNA sequencing and ATAC sequencing, we uncovered the unreported role of Prmt5 on T cells migration ability under the EAE condition. We found that mice condition knockout of Prmt5 in T cells were resistance with EAE, infiltrating inflammatory CD4+ T cells in center nervous system (CNS) were greatly reduced. However, T cells in spleen showed much more proliferation and activation properties in Prmt5cko mice, the number of pathogenic CD4+T cells in spleen were not reduced. We further revealed that Rora+CD4+T cells were elevated in Prmt5cko mice, but expressed lower level of S1pr1, resulting in a lack of CD4+ T cells egress from spleen and migrate to CNS, leading to pathogenic CD4+T cells were blocked in spleen. Moreover, single cell ATAC sequencing revealed that Klf2 were enriched in S1pr1 promoter and reduced in Prmt5cko mice. Correctively, our study delineated the undiscovered role of Prmt5 on T cell biology, Prmt5 may through Klf2-S1pr1 pathway and regulate T cells migration; modulating Prmt5 levels may be useful for controlling CD4+T cell migration in CD4+T cell mediated diseases including MS.
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Project description:NFIC1, the longest isoform of NFIC, is essential for the regulation on spatiotemporal expressions of drug-metabolizing genes in liver. However, the role of NFIC1 in breast cancer is not clear. Here we showed that increased expression of NFIC1 suppressed the migration and invasion of MCF-7 cells. The activation of interferon-associated Jak-STAT pathway was enhanced with NFIC1 overexpression. NFIC1 overexpression upregulated the expression of IFNB1, IFNL1, IFNL2 and IFNL3. Treatment with Jak-STAT pathway inhibitors, Filgotinib or Ruxolitinib, reversed the suppressive effects of NFIC1 overexpression on migration and invasion. In addition, we found that MX1 and MX2 were the target genes of NFIC1- activated Jak-STAT pathway, which mediated the migration and invasion of MCF-7 cells. These results demonstrated that NFIC1 inhibited the migration and invasion in MCF-7 cells through interferon mediated activation of Jak-STAT pathway, indicating that Jak-STAT pathway might be a potential therapeutic target for preventing breast cancer metastasis.
2023-03-01 | GSE197755 | GEO
Project description:Glioblastoma cells are characterized by a highly invasive behavior whose mechanisms are not yet understood. Using the wound healing and Boyden chamber assays we compared in the present study the migration and invasion abilities of 5 glioblastoma cell lines (DK-MG, GaMG, U87-MG, U373-MG, SNB19) differing in p53 and PTEN status. We also analyzed by Western blotting the expression of PTEN, p53, mTOR and several other marker proteins involved in cell adhesion, migration and invasion. Among 5 cell lines, GaMG cells exhibited the fastest rate of wound closure, whereas U87-MG cells showed the most rapid chemotactic migration in the Boyden chamber assay. In DK-MG and GaMG cells, F-actin mainly occurred in the numerous stress fibers spanning the cytoplasm, whereas U87-MG, U373-MG and SNB19 cells preferentially expressed F-actin in filopodia and lamellipodia. Moreover, the two glioblastoma lines mutated in both p53 and PTEN genes (U373-MG and SNB19) were found to exhibit the fastest invasion rates through the Matrigel matrix. Here, we performed a gene expression profiling of the five glioblastoma cell lines to examine the molecular framework of differences in invasive behavior to find possible targets for chemo- and radiation therapy.
2014-09-05 | E-GEOD-53124 | biostudies-arrayexpress