Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Methylation of HBP1 by PRMT1 inhibits its tumor-suppressive function through regulating 2 GSN-mediated actin cytoskeleton remodeling

ABSTRACT: HBP1 is a sequence-specific transcription factor which acts as a tumor inhibitor. HBP1 exerts tumor-suppressive function through regulating the expression of many genes during cell metabolism and cell cycle process. Posttranslational modification of HBP1 is crucial for its function. In this study, we found that HBP1 was methylated at R378 by PRMT1, which decreased 16 HBP1 protein stability by promoting its ubiquitination and proteasome-mediated degradation. PRMT1-mediated methylation of HBP1 could alleviate the repressive effects of HBP1 on tumor metastasis and growth through regulation of GSN expression. GSN was identified as a novel target gene of HBP1. Methylation of HBP1 promoted actin cytoskeleton remodeling and tumor progression by downregulating GSN levels. The methylated HBP1-GSN axis was also associated with the clinical outcomes of cancer patients. Targeting methylated HBP1-GSN axis may provide a therapeutic strategy for cancer. Significance: This investigation elucidated the mechanism of how methylation of HBP1 at R378 inhibits its tumor-suppressive function and promotes actin cytoskeleton remodeling, thus providing the strategy for targeting HBP1 during cancer treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE205932 | GEO | 2022/06/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Methylation of HBP1 by PRMT1 inhibits its tumor-suppressive function through regulating 2 GSN-mediated actin cytoskeleton remodeling

Project description:Methylation of HBP1 by PRMT1 inhibits its tumor-suppressive function through regulating 2 GSN-mediated actin cytoskeleton remodeling

| PRJNA848384 | ENA

Pseudomonas nitroreducens HBP1

Project description:Pseudomonas nitroreducens HBP1 Genome sequencing and assembly

| PRJNA232110 | ENA

HBP1 inhibits the development of type 2 diabetes mellitus through transcriptional activation of the IGFBP1 gene

Project description:Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that is highly prevalent worldwide and characterized by glucose and lipid metabolism disorders. However, the pathogenic mechanisms have not been fully established. Here, we found that HMG-box transcription factor 1 (HBP1) is involved in T2DM and that its deficiency in mice aggravates the features of diabetes. In addition, we undertook screening by RNA sequencing and found that HBP1 activates the transcription of the insulin-like growth factor binding protein 1 (IGFBP1) gene. Moreover, Insulin and palmitic acid reduced HBP1 protein expression and inhibited its binding to the IGFBP1 promoter. Furthermore, HBP1 reduced the serum free insulin-like growth factor 1 (IGF-1) concentration through IGFBP1 and inhibited the PI3K/AKT signaling pathway. This forms an insulin/HBP1/IGFBP1 negative feedback regulatory loop to dynamically regulate blood glucose and insulin concentrations. These findings have elucidated a mechanism whereby HBP1 and its negative feedback regulatory loop influence the development of T2DM, thereby providing a new theoretical basis and potential therapeutic target for T2DM.

2022-09-26 | GSE214089 | GEO

The ALK downregulated target gene HBP1 and repressor of MYCN activity as synergistic target for combined PI3K/HDAC inhibition [microarray]

Project description:ALK mutations occur in 10% of primary neuroblastoma and represent a major target for precision treatment. In combination with MYCN amplification, ALK mutations infer an ultra-high-risk phenotype with very poor prognosis. To anticipate to future precision drugging, a deeper understanding of the molecular consequences of constitutive ALK signaling and its relationship to MYCN activity in this aggressive pediatric tumor, will be essential to understand treatment responses and failure as well as to ensure improved design of drugging combinations. We show that mutant ALK downregulates the HMG-box transcription factor 1 (HBP1) through the PI3K-AKT-FOXO3a signaling axis. Interestingly, we also demonstrate that HBP1 is under control of MYCN, through negative regulation of the miR-17~92 cluster. Moreover, modulation of HBP1 in neuroblastoma negatively affect MYCN activity, including alleviating MYCN/PRC2 controlled gene repression. Combined targeting of PI3K and MYCN signaling induced strong synergistic blocking of tumor growth, thus offering potential for targeted therapeutic interventions.

2019-02-14 | GSE94811 | GEO

The ALK downregulated target gene HBP1 and repressor of MYCN activity as synergistic target for combined PI3K/HDAC inhibition [RNA-Seq]

2019-02-14 | GSE95189 | GEO

Pseudomonas nitroreducens HBP1

Project description:Pseudomonas nitroreducens HBP1, complete genome sequencing and assembly (PacBio)

| PRJNA607506 | ENA

Manuscript title: C/EBPα is methylated by PRMT1 to regulate Cyclin D1 gene transcription in human breast cancer

Project description:C/EBPα is an essential transcription factor involved in regulating the expression or function of certain cell-cycle regulators. However, little is known about the role of methylation in regulating the antiproliferation activity of C/EBPα. Here, we report that knockdown of protein arginine methyltransferases 1 (PRMT1) leads to cellular growth arrest accompanied by a decrease in Cyclin D1 gene expression in breast cancer cells. Furthermore, we reveal that C/EBPα is methylated by PRMT1 at three arginine residues (R35, R156, and R165), which impairs the interaction of C/EBPα with HDAC3 and modulates the transcription activity of C/EBPα and Cyclin D1 gene expression. PRMT1 is upregulated in human breast cancer, and elevated PRMT1 is correlated with cancer malignancy. Most importantly, a specific inhibitor of PRMT1 significantly impedes the growth of cancer cells from triple-negative breast cancer patients. Our data demonstrate that high expression of PRMT1 promotes the expression of Cyclin D1 through methylation of C/EBPα to interfere with the repressive function of HDAC3, which leads to rapid growth of tumor cells during the pathogenesis of breast cancer. This evidence that PRMT1 mediates C/EBPα methylation sheds light on a novel therapeutic pathway for breast cancer.

2020-04-05 | GSE121168 | GEO

Targeting PRMT1-mediated SRSF1 Methylation to Suppress Exon Inclusion within Oncogenic Transcripts and Breast Tumorigenesis

Project description:PRMT1 is highly expressed in breast tumors, and has been suggested to play a vital role in breast tumorigenesis, but the underlying molecular mechanisms remain to be fully characterized. Here, we reveal that PRMT1 exhibits a wide-spreading role in RNA alternative splicing based on transcriptome analysis, with a preference for exon inclusion in a large cohort of oncogenic genes. Profiling PRMT1 methylome reveals that the arginine/serine-rich splicing factor SRSF1 is heavily arginine-methylated by PRMT1, which is critical for SRSF1 phosphorylation, SRSF1 binding with RNA, and PRMT1-induced exon inclusion. In breast tumors, the overexpression of PRMT1 is associated with high levels of SRSF1 arginine methylation and aberrant exon inclusion in those oncogenic genes. Accordingly, PRMT1-mediated SRSF1 methylation and exon inclusion events are found to be critical for the malignant behaviors of breast cancer cells. Furthermore, we identified and characterized a selective PRMT1 inhibitor iPRMT1, which is potent in inhibiting PRMT1-mediated SRSF1 methylation and exon inclusion events, and breast cancer cell growth both in vitro and in vivo. Combination treatment with iPRMT1 and inhibitor targeting SRSF1 phosphorylation, SPHINX31 or SRPIN340, exhibits synergistic effects on suppressing breast cancer cell growth, strengthening the cross-talk between arginine methylation and phosphorylation in SRSF1. In conclusion, our data uncover a key mechanism underlying PRMT1-mediated gene alternative splicing, demonstrating targeting PRMT1 has great potential to treat breast cancer in clinic.

2023-10-02 | GSE212049 | GEO

Prmt1 safeguards mouse embryonic stem cells against bias toward the extraembryonic endoderm cell fate via arginine methylation of Klf4

Project description:Heterogeneous gene expression is a characteristic feature of stem cells and is essential for steering lineage choices. However, the molecular mechanisms of heterogeneity remain largely unknown. Here, we report that depletion of protein arginine methyltransferase 1 (Prmt1) in mouse embryonic stem (ES) cells heterogeneously induces the expression of primitive endoderm (PrE) genes, consequently biasing the cells to fluctuate toward the extraembryonic endoderm stem (XEN) cell fate. Furthermore, the pluripotency factor Klf4 is arginine-methylated by Prmt1 at arginine 396 (R396), which is required for recruitment of the mSin3a/HDAC complex to silence PrE genes. Importantly, when methylation is disrupted by a Prmt1 knockout, a Prmt1 inhibitor, or a blocked methylation site in Klf4, ES cells are predisposed to XEN induction. Our data demonstrate the importance of Prmt1 in the fluctuating heterogeneity of ES cells and reveal a regulatory mechanism for cell fate decisions that is centered on Klf4 methylation mediated by Prmt1.

2021-12-27 | GSE124920 | GEO

Characterization of N6-methyladenosine in the testis tissue of cattle-yak

Project description:N6-methyladenosine (m6A) is the most prominent mRNA modification in eukaryotes, and its potential regulatory role has recently been identified in mammals, plants, and yeast. However, how m6A methylation regulates spermatogenesis remains unknown. In this study, cattle-yak testis tissue was used as the experimental material, and the m6A map was generated through preliminary experiments and methylated RNA immunoprecipitation sequencing. Only spermatogonia and Sertoli cells were observed in cattle-yak testis tissue. Experiments examining the expression of methylation-related enzymes and the overall methylation level showed that the methylation level in the testis of the cattle-yak was slightly lower than that of the sexually mature yak, but significantly higher than that of the pre-sexually mature yak. Annotation analysis indicated that differentially methylated peaks were most frequently concentrated in exonic regions, followed by 3'UTR and finally 5'UTR regions. Through enrichment analysis of differentially expressed genes and differentially methylated corresponding genes, GO analysis of T-vs-Y group mainly involved spermatogenesis, including cytoskeleton, actin binding, etc. KEGG analysis showed that the differential genes were mainly enriched in actin cytoskeleton regulation and MAPK signaling pathway. GO analysis of the T-vs-M group mainly involved protein ubiquitination, ubiquitin ligase complexes, ubiquitin-dependent protein catabolism and endocytosis. KEGG analysis mainly involved apoptosis and Fanconi anemia pathways. This study will lay the foundation for elucidating the molecular mechanism of m6A in male sterility of cattle-yak.

2022-06-12 | GSE205649 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data