Identification of high-risk PHF19 expressing cells in myeloma single cell multiomics
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PROVIDER: PRJNA942021 | ENA |
REPOSITORIES: ENA
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Project description:Identification of high-risk PHF19 expressing cells in myeloma single cell multiomics
| PRJNA942022 | ENA
Project description:We here report a PRC2-associated cofactor, PHD finger protein 19 (PHF19, also known as Polycomb-like 3), as a crucial mediator of tumorigenicity in multiple myeloma (MM). Using various MM models, we demonstrated a critical requirement of PHF19 for tumor growth in vitro and in vivo. Mechanistically, PHF19-mediated oncogenic effect relies on its PRC2-interacting and chromatin-binding functions. ChIP-Seq profiling showed a critical role for PHF19 in maintaining the H3K27me3 landscape. PHF19 depletion led to loss of broad H3K27me3 domains possibly due to impaired H3K27me3 spreading from CpG islands
2019-08-31 | GSE135890 | GEO
Project description:To determine the effect of overexpression PHF19 in ARP1 myeloma cells Drug resistance is a major reason for the recurrence of multiple myeloma (MM). In addition to genetic mutations, epigenetic abnormalities are involved in the whole process of MM relapse and drug resistance. In this study, we investigate the roles of polycomb like protein 19 (PHF19), a critical gene involved in the epigenetic regulation of gene expression, in the development of MM. The gene expression profiling (GEP) data shows that PHF19 is significantly up-regulated in MM cells and associated with shortened progression-free survival and overall survival in MM patients. PHF19 promotes MM cell growth both in vitro and in a subcutaneous xenograft mouse model. Up-regulated PHF19 is also associated with the development of resistance to multiple drugs, including bortezomib, in MM cells. Moreover, miR-15a can directly target PHF19 by binding to its 3'-UTR. Since miR-15a is down-regulated in MM cells, PHF19 is considered to be up-regulated due to loss of the suppression by miR-15a. The mechanistic investigations indicate that PHF19 can activate AKT which in turn leads to an increase in the phosphorylation of EZH2, a core component of PRC2 that mediates the histone H3K27 methylation. Subsequently suppresses histone H3K27 methylation and causes up-regulated expression of several anti-apoptotic genes, including BCL-xL, MCL-1 and HIF-1alpha. Moreover, PDK1 activation is significantly increased in PHF19 overexpressing MM cells.
2020-03-31 | GSE128406 | GEO
Project description:Dysregulation of Polycomb Repressive Complex 2 (PRC2) promotes oncogenesis partly through its enzymatic function for inducing tri-methylation of histone H3 lysine 27 (H3K27me3). However, it remains to be determined how PRC2 activity is regulated in normal and diseased settings. We here report a PRC2-associated cofactor, PHD finger protein 19 (PHF19, also known as Polycomb-like 3), as a crucial mediator of tumorigenicity in multiple myeloma (MM). Overexpression and/or genomic amplification of PHF19 is found associated with malignant progression of MM and plasma cell leukemia, correlating to worse treatment outcomes. Using various MM models, we demonstrated a critical requirement of PHF19 for tumor growth in vitro and in vivo. Mechanistically, PHF19-mediated oncogenic effect relies on its PRC2-interacting and chromatin-binding functions. ChIP-Seq profiling showed a critical role for PHF19 in maintaining the H3K27me3 landscape. PHF19 depletion led to loss of broad H3K27me3 domains possibly due to impaired H3K27me3 spreading from CpG islands, which is reminiscent to the reported effect of an ‘onco’-histone mutation, H3K27-to-methionine (H3K27M). RNA-Seq-based transcriptome profiling in MM lines also demonstrated a requirement of PHF19 for optimal silencing of PRC2 targets, which include cell cycle inhibitors and interferon-JAK-STAT signaling genes critically involved in tumor suppression.
2019-08-31 | GSE136410 | GEO
Project description:To investigate the transcriptomic effect of PHF19 overexpression in MM cells. We then performed gene expression profiling analysis using data obtained from RNA-seq of AMO1 cells with differential PHF19 expression.
2023-01-31 | GSE224200 | GEO
Project description:The role of PHF19 in promoting H3K27me3 deposition in multiple myeloma
| PRJNA560497 | ENA
Project description:Effect of overexpression of PHF19 in multiple myeloma cells [RNA-seq]
| PRJNA930064 | ENA
Project description:PCL family protein Phf19/Pcl3 is one of the accessory components of the PRC2 core complex, and Phf19 is highly expressed in murine ES cells and an ES cell-like embryonic carcinoma cell line, F9 cells. Here we performed microarray analysis of embryonal carcinoma cell line F9 following Phf19 knockdown by shRNA. Knocking down Phf19/Pcl3 in F9 embryonic cells led to derepression of numerous PRC2 direct target genes. 4 sampels including 2 shRNA vector control cell lines and 2 shPhf19 cell lines were used for RNA extraction and Affymetrix mouse 430 2.0 arrays.
2012-12-20 | E-GEOD-42463 | biostudies-arrayexpress
Project description:Multiple Myeloma is an incurable plasma cell malignancy with a poor survival rate that is usually treated with immunomodulatory drugs (iMiDs) and proteosome inhibitors (PIs). The malignant plasma cells quickly become resistant to these agents causing relapse and uncontrolled growth of resistant clones. From whole genome sequencing (WGS) and RNA sequencing (RNA-seq) studies, different high-risk translocation, copy number, mutational, and transcriptional markers have been identified. One of these markers, PHF19, epigenetically regulates cell cycle and other processes and has already been studied using RNA-seq. In this study a massive (325,025 cells and 49 patients) single cell multiomic dataset was generated with jointly quantified ATAC- and RNA-seq for each cell and matched genomic profiles for each patient. We identified an association between one plasma cell subtype with myeloma progression that we have called relapsed/refractory plasma cells (RRPCs). These cells are associated with 1q alterations, TP53 mutations, and higher expression of PHF19. We also identified downstream regulation of cell cycle inhibitors in these cells, possible regulation of the transcription factor (TF) PBX1 on 1q, and determined that PHF19 may be acting primarily through this subset of cells.
2024-01-31 | GSE254307 | GEO
Project description:Intratumor heterogeneity as a clinical challenge becomes most evident after several treatment lines, when multidrug-resistant subclones accumulate. To address this challenge, the characterization of resistance mechanisms at the subclonal level is key to identify common vulnerabilities. In this study, we integrate whole-genome sequencing, single-cell (sc) transcriptomics (scRNA sequencing), and chromatin accessibility (scATAC sequencing) together with mitochondrial DNA mutations to define subclonal architecture and evolution for longitudinal samples from 15 patients with relapsed or refractory multiple myeloma. We assess transcriptomic and epigenomic changes to resolve the multifactorial nature of therapy resistance and relate it to the parallel occurrence of different mechanisms: (1) preexisting epigenetic profiles of subclones associated with survival advantages, (2) converging phenotypic adaptation of genetically distinct subclones, and (3) subclone-specific interactions of myeloma and bone marrow microenvironment cells. Our study showcases how an integrative multiomics analysis can be applied to track and characterize distinct multidrug-resistant subclones over time for the identification of molecular targets against them.
2023-08-01 | GSE235783 | GEO