Protein arginine methyltransferase 6 drives endocrine resistance in breast cancer: ERα and NFkB signalling directly regulate PRMT6 expression
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA431352 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6505790.fastq.gz | Fastqsanger.gz | |||
| SRR6505800.fastq.gz | Fastqsanger.gz | |||
| SRR6505791.fastq.gz | Fastqsanger.gz | |||
| SRR6505801.fastq.gz | Fastqsanger.gz | |||
| SRR6505792.fastq.gz | Fastqsanger.gz |
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Project description:Gain- and Loss-of-function coupled with RNA-seq revealed that PRMT6 is involved in pathways drives breast carcinogenesis.
2021-01-24 | GSE109537 | GEO
Project description:Purpose: Dysregulation of histone H3 arginine (R) methylation is still unknown in primary cancer including gastric cancer (GC), although PRMT6 plays a role in asymmetric dimethylation at H3R2 (H3R2me2as) in cancer cells. The objective is to clarify biological and molecular roles of H3R2me2as-PRMT6 pathway in GC. Experimental Design: We assessed H3R2me2as and PRMT6 levels in 133 primary GC tissues by immunohistochemistry. We analyzed biological functions of PRMT6 in GC cell lines using a lentivirus overexpression and CRISPR/Cas9-based knockout of PRMT6 systems. Results: Increased H3R2me2as was found in 68 GC (51.1%) cases and independently correlated with poor prognosis. PRMT6 was overexpressed in 70 (52.6%) GC, which strongly correlated with the H3R2me2as levels (P<0.001). PRMT6 overexpression in GC cells enhanced global H3R2me2as levels, cell invasiveness in vitro, while PRMT6-knockout GC cells suppressed these effects. PRMT6 knockout also impaired tumorigenicity in vivo. Microarray and ChIP assays demonstrated that PRMT6-knockout GC cells decreased the H3R2me2as levels at the promoter regions of PCDH7, SCD and IGFBP5, resulting in up-reregulation of their gene expression. PRMT6 recruited at the regions of PCDH7 and SCD in the PRMT6-overexpressed cells. Knockdown of tumor suppressor PCDH7 in PRMT6-knockout GC cells elevated cell migration and invasion. PRMT6 expression inversely correlated with PCDH7 expression in primary GC (P=0.021). Conclusions: H3R2me2as is a strong prognostic indicator of GC patients. Global and gene-specific H3R2me2as are maintained by PRMT6. PRMT6-overexpressed GC cells may acquire invasiveness through direct inhibition of PCDH7 by increasing H3R2me2as activity. Thus, PRMT6-H3R2me2as pathway is a promising new therapeutic target in GC.
2020-04-16 | GSE113189 | GEO
Project description:Purpose: Dysregulation of histone H3 arginine (R) methylation is still unknown in primary cancer including gastric cancer (GC), although PRMT6 plays a role in asymmetric dimethylation at H3R2 (H3R2me2as) in cancer cells. The objective is to clarify biological and molecular roles of H3R2me2as-PRMT6 pathway in GC. Experimental Design: We assessed H3R2me2as and PRMT6 levels in 133 primary GC tissues by immunohistochemistry. We analyzed biological functions of PRMT6 in GC cell lines using a lentivirus overexpression and CRISPR/Cas9-based knockout of PRMT6 systems. Results: Increased H3R2me2as was found in 68 GC (51.1%) cases and independently correlated with poor prognosis. PRMT6 was overexpressed in 70 (52.6%) GC, which strongly correlated with the H3R2me2as levels (P<0.001). PRMT6 overexpression in GC cells enhanced global H3R2me2as levels, cell invasiveness in vitro, while PRMT6-knockout GC cells suppressed these effects. PRMT6 knockout also impaired tumorigenicity in vivo. Microarray and ChIP assays demonstrated that PRMT6-knockout GC cells decreased the H3R2me2as levels at the promoter regions of PCDH7, SCD and IGFBP5, resulting in up-reregulation of their gene expression. PRMT6 recruited at the regions of PCDH7 and SCD in the PRMT6-overexpressed cells. Knockdown of tumor suppressor PCDH7 in PRMT6-knockout GC cells elevated cell migration and invasion. PRMT6 expression inversely correlated with PCDH7 expression in primary GC (P=0.021). Conclusions: H3R2me2as is a strong prognostic indicator of GC patients. Global and gene-specific H3R2me2as are maintained by PRMT6. PRMT6-overexpressed GC cells may acquire invasiveness through direct inhibition of PCDH7 by increasing H3R2me2as activity. Thus, PRMT6-H3R2me2as pathway is a promising new therapeutic target in GC.
2020-04-16 | GSE113188 | GEO
Project description:ES cells are able to self-renew and remain pluripotent. These characteristics are maintained by both genetic and epigenetic regulators. Protein arginine methyltransferase (PRMT) 4 and 5 are shown to be important in early embryonic development and in ES cells. PRMT6-mediated di-methylation of histone H3 at arginine 2 (H3R2me2) can antagonize the tri-methylation of histone H3 at lysine 4, which marks active genes. However, it is unclear whether PRMT6 and PRMT6-mediated H3R2me2 play crucial roles in early embryonic development and ES cell identity. In this study, we investigate their functions using mouse ES cells as the model. We used microarray (Affymetrix GeneChip Mouse Gene 1.0ST) to examine the global change of gene expression in mouse ES cells when Prmt6 was overexpressed and identified distinct classes of genes that are up-regulated and down-regulated during this process. Mouse ES cells were transfected with either pCAGIP.puro empty vector (control) or Prmt6 overexpressing plasmid (P+6 OE). After 3 days of selection by puromycin, cells from both populations were subjected to RNA extraction and hybridization on Affymetrix microarrays.
2011-03-04 | E-GEOD-27685 | biostudies-arrayexpress
Project description:Protein arginine methyltransferase 6 (PRMT6) is an epigenetic regulator of fundamental cellular processes, such as gene expression and DNA repair. Asymmetric dimethylation of histone H3 at arginine 2 (H3R2me2a) is the major histone modification catalyzed by PRMT6. To identify the genome-wide deposition and transcriptional impact of H3R2me2a, we established PRMT6 deletion in a human cell model of neural differentiation. These knockout cells show severe neural differentiation defects. ChIP-seq profiling reveals that H3R2me2a is present at promoter as well as non-promoter sites in a PRMT6-dependent manner. Loss of H3R2me2a causes enhanced H3K4me3 deposition and target gene transcription supporting a genome-wide repressive nature of H3R2me2a. Intriguingly, the non-promoter H3R2me2a peaks co-localize with active enhancer marks, such as H3K4me1 and H3K27ac.
2018-09-27 | GSE107609 | GEO
Project description:PRMT6, a type I arginine methyltransferase, di-methylates the arginine residues of both histones and non-histones asymmetrically. Increasing evidence indicates that PRMT6 plays a tumor mediator involved in human malignancies. Here, we aim to uncover the essential role and underlying mechanisms of PRMT6 in promoting glioblastoma (GBM) proliferation. Investigation of PRMT6 expression in glioma tissues demonstrated that PRMT6 is overexpressed, and elevated expression of PRMT6 is negatively correlated with poor prognosis in glioma/GBM patients. Silencing PRMT6 inhibited GBM cell proliferation and induced cell cycle arrest at the G0/G1 phase, while overexpressing PRMT6 had opposite results. Further, we found that PRMT6 attenuates the protein stability of CDKN1B by promoting its degradation. Subsequent mechanistic investigations showed that PRMT6 maintains the transcription of CDC20 by activating histone methylation mark (H3R2me2a), and CDC20 interacts with and destabilizes CDKN1B. Rescue experimental results confirmed that PRMT6 promotes the ubiquitinated degradation of CDKN1B and cell proliferation via CDC20. We also verified that the PRMT6 inhibitor (EPZ020411) could attenuate the proliferative effect of GBM cells. Our findings illustrate that PRMT6, an epigenetic mediator, promotes CDC20 transcription via H3R2me2a to mediate the degradation of CDKN1B to facilitate GBM progression. Targeting PRMT6-CDC20-CDKN1B axis might be a promising therapeutic strategy for GBM.
2023-03-31 | GSE221971 | GEO
Project description:Protein arginine methyltransferase 6 (PRMT6) is an epigenetic regulator of fundamental cellular processes, such as gene expression and DNA repair. Asymmetric dimethylation of histone H3 at arginine 2 (H3R2me2a) is the major histone modification catalyzed by PRMT6. To identify the genome-wide deposition and transcriptional impact of H3R2me2a, we established PRMT6 deletion in a human cell model of neural differentiation. These knockout cells show severe neural differentiation defects. ChIP-seq profiling reveals that H3R2me2a is present at promoter as well as non-promoter sites in a PRMT6-dependent manner. Loss of H3R2me2a causes enhanced H3K4me3 deposition and target gene transcription supporting a genome-wide repressive nature of H3R2me2a. Intriguingly, the non-promoter H3R2me2a peaks co-localize with active enhancer marks, such as H3K4me1 and H3K27ac.
2018-09-27 | GSE117341 | GEO
Project description:Histone modification, a major epigenetic mechanism which regulates gene expression by chromatin remodeling, introduces dynamic changes in chromatin architecture. Protein arginine methyltransferase 6 (PRMT6) is overexpressed in various types of cancers. Epigenome regulates the expression of endogenous retrovirus (ERV), which activates interferon signaling related to cancer. We investigated the antitumor effects of PRMT6 inhibition and the role of PRMT6 in endometrial cancer (EC), using epigenome multi-omics analysis including assay for chromatin immunoprecipitation sequencing (ChIP-seq) and ribonucleic acid sequencing (RNA-seq). The expression of PRMT6 in EC was analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). The prognostic impact of PRMT6 expression was evaluated using IHC. We investigated the effects of PRMT6-knockdown (KD) using cell viability and apoptosis assays, as well as its effects on the epigenome using ChIP-seq of H3K27ac antibodies and RNA-seq. Finally, we evaluated the downstream targets identified by multi-omics analysis. PRMT6 was overexpressed in EC and associated with a poor prognosis. PRMT6-KD induced histone hypomethylation, while suppressing cell growth and apoptosis. ChIP-seq revealed that PRMT6 regulated genomic regions related to interferons and apoptosis through histone modifications. RNA-seq data showed altered interferon-related pathways and increased expression of tumor suppressor genes, such as NKX6-1 and PIK3R1, after PRMT6-KD. RT-qPCR showed that eight ERV genes which activated interferon signaling were upregulated by PRMT6-KD. Our data suggested that PRMT6 inhibition induced apoptosis through interferon signaling activated by ERV. PRMT6 regulated tumor suppressor genes and may be a novel therapeutic target in EC.
2024-02-07 | GSE239295 | GEO
Project description:Histone modification, a major epigenetic mechanism which regulates gene expression by chromatin remodeling, introduces dynamic changes in chromatin architecture. Protein arginine methyltransferase 6 (PRMT6) is overexpressed in various types of cancers. Epigenome regulates the expression of endogenous retrovirus (ERV), which activates interferon signaling related to cancer. We investigated the antitumor effects of PRMT6 inhibition and the role of PRMT6 in endometrial cancer (EC), using epigenome multi-omics analysis including assay for chromatin immunoprecipitation sequencing (ChIP-seq) and ribonucleic acid sequencing (RNA-seq). The expression of PRMT6 in EC was analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). The prognostic impact of PRMT6 expression was evaluated using IHC. We investigated the effects of PRMT6-knockdown (KD) using cell viability and apoptosis assays, as well as its effects on the epigenome using ChIP-seq of H3K27ac antibodies and RNA-seq. Finally, we evaluated the downstream targets identified by multi-omics analysis. PRMT6 was overexpressed in EC and associated with a poor prognosis. PRMT6-KD induced histone hypomethylation, while suppressing cell growth and apoptosis. ChIP-seq revealed that PRMT6 regulated genomic regions related to interferons and apoptosis through histone modifications. RNA-seq data showed altered interferon-related pathways and increased expression of tumor suppressor genes, such as NKX6-1 and PIK3R1, after PRMT6-KD. RT-qPCR showed that eight ERV genes which activated interferon signaling were upregulated by PRMT6-KD. Our data suggested that PRMT6 inhibition induced apoptosis through interferon signaling activated by ERV. PRMT6 regulated tumor suppressor genes and may be a novel therapeutic target in EC.
2024-02-07 | GSE239294 | GEO
Project description:Our data reveal that RNA m6A displays a sharp transition during leukemogenesis and involves in acquiring stem cell properties of leukemia stem cells (LSCs). We find that m6A reader IGF2BP2 and protein arginine methyltransferase PRMT6 play key roles in the acquisition of LSCs properties. Genetical deletion and pharmacological inhibition of PRMT6 delayed AML development. Mechanistically, IGF2BP2 regulates PRMT6 expression by stabilizing its mRNA in an m6A-dependent manner. PRMT6 further suppresses the expression of lipid transporter MFSD2A by establishing inactive H3R2me2a in its promoter region. Loss of PRMT6 and IGF2BP2 upregulates the expression of MFSD2A that increases the uptake of docosahexaenoic acid. Collectively, our findings uncover a critical role of IGF2BP2-PRMT6-MFSD2A signaling axis in AML development, and provide a promising therapeutic strategy for targeting LSCs.
2023-06-20 | GSE210279 | GEO