PRMT5 knockdown changes gene expression in prostate cancer cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE117596 | GEO | 2023/12/25
REPOSITORIES: GEO
Similar Datasets
Project description:Prostate cancer (PCa) is the most frequently diagnosed malignancy in men worldwide. Epigenetic regulation has been recognized as a main mechanism of cancer evolution. PRMT5 is the major type II protein arginine methyltransferase catalyzing the symmetric dimethylation of arginine, and METTL3 is the enzymatic component of the large N6-adenosine-methyltransferase complex in mammalian responsible for N6-methyladenosine (m6A) modification in diverse RNA species. Both genes are found upregulated in PCa. However, their exact functional contribution to prostate tumorigenesis is unknown. As both proteins can regulate transcription via binding to chromatin, we seek to explore their DNA binding profiles in both AR+ LNCaP and AR- PC3 cells via recently developed CUT&Tag technique. Antibodies we used were Active Motif #61001 for PRMT5 and Abcam #195352 for METTL3. Our data suggests that both proteins regulate PCa cell biology, at least partially, through chromatin-binding and subsequent transcriptional regulation. CUT&Tag assay for arginine methyltransferase PRMT5 and N6‐adenosine‐methyltransferase METTL3 in LNCaP and PC3 cells
2024-09-03 | GSE217412 | GEO
Project description:Compared to intensely studied DNA methylation, protein methylation is less studied. PRMT5 is the major type II protein arginine methyltransferase catalyzing the symmetric dimethylation of arginine. Recent reports have indicated that PRMT5 is overexpressed in multiple cancer types, including prostate. However, the exact contribution of PRMT5 to prostate tumorigenesis is unknown. To explore PRMT5 in prostate cancer (PCa) therapeutically, we utilized a recently developed selective small molecule PRMT5 inhibitor (PRMT5i, EPZ015666) that has shown in vivo potency in MCL models. To understand the molecular mechanisms of action of PRMT5i in PCa, we performed deep RNA-seq analysis in PC3 and LNCaP cells treated with or without PRMT5i at 4 μM for 4 days in vitro.
2023-12-25 | GSE114151 | GEO
Project description:Prostate cancer (PCa) is the most frequently diagnosed malignancy in men worldwide. Epigenetic regulation has been recognized as a main mechanism of cancer evolution. PRMT5 is the major type II protein arginine methyltransferase catalyzing the symmetric dimethylation of arginine in mammalian. PRMT5 is found upregulated in PCa. However, its exact functional contribution to prostate tumorigenesis is unknown. PRMT5 inhibition via pharmacological inhibition (EPZ015666) reduces stemness with paralleled differentiation and arrests cell cycle progression but without causing appreciable apoptosis.To understand the mechanisms of cell tolerance to PRMT5 inhibition and to identify potential pathways that function synergistically with EPZ015666, we performed a genome-wide CRISPR/Cas9 loss-of-function screen in the presence of EPZ015666. Our data unravel that many clinical-grade drugs of known oncogenic pathways can be repurposed to target castration-resistant PCa when used in synergy with EPZ015666 at low doses. Genome-wide CRISPR/Cas9 loss-of-function screen in the presence of EPZ015666 in DU145
2024-09-03 | GSE222018 | GEO
Project description:Prostate cancer (PCa) is the most frequently diagnosed malignancy in men worldwide. miRNAs play nonnegligible function in PCa progression. Although several groups studied the effect of miR-375 on PCa phenotypes, some controversial findings emerged. Here, we seek to explore the effect of miR-375 on transcriptome profile in both AR+ LNCaP and AR- PC3 cells via RNA-seq.
2024-03-01 | GSE234110 | GEO
Project description:PRMT5 is a methyltransferase that catalyzes symmetric dimethylation of arginine residues in histones (H4R3, H3R8, H3R2, and H2AR3) to regulate transcription of target genes. While PRMT5 is generally considered an epigenetic repressor, recent evidence from our lab and others demonstrate that PRMT5 also functions as an epigenetic activator. Although in vitro biochemical studies suggest that the PRMT5 interacting proteins methylosome protein 50 (MEP50) and methylosome subunit pICln enhance PRMT5 enzymatic activity, how these interacting proteins cooperate with PRMT5 to regulate gene transcription in vivo remains to be elucidated. Here we perform RNA-seq analysis of prostate cancer cells 22Rv1 with knockdown of PRMT5, MEP50, and pICln, in order to elucidate how these proteins control transcriptome.
2022-05-05 | GSE154951 | GEO
Project description:Protein Arginine Methyltransferase (PRMT) 5 is the major type 2 methyltransferase catalyzing symmetric dimethylation (SDM) of arginine. PRMT5 inhibition or deletion in CD4 Th cells reduces TcR engagement-induced IL-2 production and Th cell expansion and confers protection against experimental autoimmune encephalomyelitis (EAE), the animal model of Multiple Sclerosis. However, the mechanisms by which PRMT5 modulates T helper (Th) cell proliferation are still not completely understood and neither are the methylation targets in T cells. In this manuscript, we uncover the role of PRMT5 on alternative splicing (AS) in activated T cells and identify several targets of PRMT5 SDM involved in splicing. In addition, we find a possible link between PRMT5 mediated AS of Trpm4 (Transient Receptor Potential Cation Channel Subfamily M Member 4) and TcR/NFAT signaling/IL-2 production. This understanding may guide development of drugs targeting these processes to benefit patients with T cell-mediated diseases.
2021-10-01 | GSE181931 | GEO
Project description:PRMT5 is important for gliomas, however its physiological function in oligodendrocyte progenitors (OPCs), remains poorly understood. Here we report PRMT5 to be responsible for symmetric di-methylation of histone H4R3 (H4R3me2s) in OPC. PRMT5 depletion via CRISPR/Cas9 decreased H4R3me2s, altered the OPC transcriptome, and decreased OPC survival. Strikingly, these changes were associated with a marked increase of H4K5ac in OPC, but not in gliomas. Consistently, ChIP-sequencing analysis revealed increased genome-wide distribution of H4K5ac in PRMT5 knockout cells. In vitro acetylation assays demonstrated reciprocal inhibition between symmetric arginine methylation and lysine acetylation. Low H4R3me2s and high H4K5ac levels were also detected in OPC in mice with lineage-specific ablation of Prmt5 (Olig1-Cre;Prmt5fl/fl), resulting in severely impaired developmental myelination. Importantly, pharmacological inhibition of acetyltransferase activity partially rescued the effect of Prmt5 deletion on oligodendrocyte-specific gene transcripts. Collectively, we identify PRMT5 as a critical modulator of histone acetylation and OPC differentiation in early developmental myelination.
2018-06-02 | GSE94067 | GEO
Project description:AKT is involved in a number of key cellular processes including cell proliferation, apoptosis and metabolism. Hyperactivation of AKT is associated with many pathological conditions, particularly cancers. Emerging evidence indicates that arginine methylation is involved in modulating AKT signaling pathway. However, whether and how arginine methylation directly regulates AKT kinase activity remain unknown. Here we report that protein arginine methyltransferase 5 (PRMT5), but not other PRMTs, promotes AKT activation by catalyzing symmetric dimethylation of AKT1 at arginine 391 (R391). Mechanistically, AKT1-R391 methylation cooperates with phosphatidylinositol 3,4,5 trisphosphate (PIP3) to relieve the pleckstrin homology (PH)-in conformation, leading to AKT1 membrane translocation and subsequent activation by phosphoinositide-dependent kinase-1 (PDK1) and the mechanistic target of rapamycin complex 2 (mTORC2). As a result, deficiency in AKT1-R391 methylation significantly suppresses AKT1 kinase activity and tumorigenesis. Lastly, we show that PRMT5 inhibitor synergizes with AKT inhibitor or chemotherapeutic drugs to enhance cell death. Altogether, our study suggests that R391 methylation is an important step for AKT activation and its oncogenic function.
2022-02-17 | PXD026071 | Pride
Project description:In immunosurveillance, bone-derived immune cells infiltrate the tumor and secrete inflammatory cytokines to destroy cancer cells. However, cancer cells have evolved mechanisms to usurp inflammatory cytokines to promote tumor progression. In particular, the inflammatory cytokine, interleukin-1 (IL-1), is elevated in prostate cancer (PCa) patient tissue and serum and promotes PCa bone metastasis. IL-1 also represses androgen receptor (AR) accumulation and activity in PCa cells, yet the cells remain viable; suggesting that IL-1 may also contribute to AR-targeted therapy resistance. Furthermore, IL-1 and AR protein levels negatively correlate in PCa tumor cells. Taken together, we hypothesize that IL-1 reprograms AR positive (AR+) PCa cells into AR negative (AR-) PCa cells that co-opt IL-1 signaling to ensure AR-independent survival in the inflammatory tumor microenvironment. Thus, we employed RNA sequencing to identify pathways that are modulated by IL-1 concomitant with IL-1-induced AR repression in PCa cells. Comparative analysis of sequencing data from the AR+ LNCaP PCa cell line versus the AR- PC3 PCa cell line reveals an IL-1-conferred gene suite in LNCaP cells that is constitutive in PC3 cells, and includes AR and AR target gene repression and the induction of prosurvival, lineage, and cancer stem cell genes. Bioinformatics analysis of the IL-1 regulated gene suite revealed that inflammatory and immune response pathways are primarily elicited; likely facilitating PCa cell survival in an inflammatory tumor microenvironment. Our data supports that IL-1 reprograms AR+ PCa cells to mimic AR- PCa gene expression patterns that favor AR-targeted treatment resistance and cell survival.
2018-02-01 | GSE105088 | GEO
Project description:MiRNAs are small non-coding RNAs that regulate the expression of specific mRNA targets mainly by translational repression, mRNA deadenylation or cleavage. This series is meant to identify miRNAs deregulated in prostate cancer (PCa) by comparing the PCa cell lines LNCaP, PC3 and Du-145 to the normal prostate epithelial cell line RWPE-1. We analyzed three arrays each for LNCaP, PC3, Du-145 and RWPE-1 cell lines
2012-03-08 | E-GEOD-17317 | biostudies-arrayexpress