The impact of small molecule inhibition of METTL3 on normal haematopoiesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA950362 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We performed scRNA-seq on haematoietic stem and progenitor cells of healthy wild-type mice treated with the small-molecule inhibitor of METTL3, STM2457.
2023-07-20 | GSE228562 | GEO
Project description:The N6-methyladenosine (m6A) RNA modification is an important regulator of gene expression. m6A is deposited by a methyltransferase complex that includes methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14). High levels of METTL3 and METTL14 drive the growth of many types of adult cancer, and METTL3/METTL14 inhibitors are emerging as new anticancer agents. However, little is known about the m6A epitranscriptome or the role of the METTL3/METTL14 complex in neuroblastoma, a common pediatric cancer. Here, we show that METTL3 knockdown or pharmacologic inhibition with the small molecule STM2457 leads to reduced neuroblastoma cell proliferation and increased differentiation. These changes in neuroblastoma phenotype were associated with decreased m6A deposition on transcripts involved in nervous system development and neuronal differentiation and increased stability and expression of target mRNAs. In preclinical studies, STM2457 treatment suppressed the growth of neuroblastoma tumors in vivo. Together, these results support the potential of METTL3/METTL14 complex inhibition as therapeutic strategy against neuroblastoma.
2024-04-10 | GSE240582 | GEO
Project description:The N6-methyladenosine (m6A) RNA modification is an important regulator of gene expression. m6A is deposited by a methyltransferase complex that includes methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14). High levels of METTL3 and METTL14 drive the growth of many types of adult cancer, and METTL3/METTL14 inhibitors are emerging as new anticancer agents. However, little is known about the m6A epitranscriptome or the role of the METTL3/METTL14 complex in neuroblastoma, a common pediatric cancer. Here, we show that METTL3 knockdown or pharmacologic inhibition with the small molecule STM2457 leads to reduced neuroblastoma cell proliferation and increased differentiation. These changes in neuroblastoma phenotype were associated with decreased m6A deposition on transcripts involved in nervous system development and neuronal differentiation and increased stability and expression of target mRNAs. In preclinical studies, STM2457 treatment suppressed the growth of neuroblastoma tumors in vivo. Together, these results support the potential of METTL3/METTL14 complex inhibition as therapeutic strategy against neuroblastoma.
2024-04-10 | GSE263118 | GEO
Project description:The N6-methyladenosine (m6A) RNA modification is an important regulator of gene expression. m6A is deposited by a methyltransferase complex that includes methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14). High levels of METTL3 and METTL14 drive the growth of many types of adult cancer, and METTL3/METTL14 inhibitors are emerging as new anticancer agents. However, little is known about the m6A epitranscriptome or the role of the METTL3/METTL14 complex in neuroblastoma, a common pediatric cancer. Here, we show that METTL3 knockdown or pharmacologic inhibition with the small molecule STM2457 leads to reduced neuroblastoma cell proliferation and increased differentiation. These changes in neuroblastoma phenotype were associated with decreased m6A deposition on transcripts involved in nervous system development and neuronal differentiation and increased stability and expression of target mRNAs. In preclinical studies, STM2457 treatment suppressed the growth of neuroblastoma tumors in vivo. Together, these results support the potential of METTL3/METTL14 complex inhibition as therapeutic strategy against neuroblastoma.
2024-04-10 | GSE240581 | GEO
Project description:The N6-methyladenosine (m6A) RNA modification is an important regulator of gene expression. m6A is deposited by a methyltransferase complex that includes methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14). High levels of METTL3 and METTL14 drive the growth of many types of adult cancer, and METTL3/METTL14 inhibitors are emerging as new anticancer agents. However, little is known about the m6A epitranscriptome or the role of the METTL3/METTL14 complex in neuroblastoma, a common pediatric cancer. Here, we show that METTL3 knockdown or pharmacologic inhibition with the small molecule STM2457 leads to reduced neuroblastoma cell proliferation and increased differentiation. These changes in neuroblastoma phenotype were associated with decreased m6A deposition on transcripts involved in nervous system development and neuronal differentiation and increased stability and expression of target mRNAs. In preclinical studies, STM2457 treatment suppressed the growth of neuroblastoma tumors in vivo. Together, these results support the potential of METTL3/METTL14 complex inhibition as therapeutic strategy against neuroblastoma.
2024-04-10 | GSE262731 | GEO
Project description:To study the effect of m6A modifications on subcellular mRNA localization we depleted m6A writer Mettl3 with shRNA and small molecule from mouse primary cortical neurons (mPCN) and sequenced neuritic and somatic compartments in parallel with scrambled shRNA control.
2023-07-12 | E-MTAB-11570 | biostudies-arrayexpress
Project description:Small-molecule Inhibition of METTL3 Suppresses Tumor Growth and Promotes Neuroblastoma Differentiation
| PRJNA1004276 | ENA
Project description:Background: N6-methyladenosine (m6A) RNA modification plays a crucial role in various biological events and is implicated in various metabolic-related diseases. However, its role in MASLD remains unclear. This study aims to investigate the impact of Mettl3 on MASLD through multi-omics analysis, with a focus on exploring its potential mechanisms of action. Methods: MASLD mouse models were established by feeding a high-fat diet for 12 weeks, and Mettl3 stable overexpression AML12 cell models were constructed via lentiviral transfection. Subsequent transcriptomic and proteomic analyses, as well as integrated analysis between different omics datasets, were conducted. Results: Mettl3 expression significantly increased in MASLD mouse models. In the transcriptomic and proteomic analyses, we identified 848 genes with significant inconsistencies between transcriptomic and proteomic datasets. GO/KEGG enrichment terms may involve post-transcriptional modifications, particularly Mettl3-mediated m6A modification. Subsequently, through integrated proteomic analysis of Mettl3-overexpressed AML12 cell models and MASLD mouse models, we selected the top 20 co-upregulated and co-downregulated GO/KEGG terms as the main biological processes influenced by Mettl3 in MASLD. By intersecting with pathways obtained from previous integrated analyses, we identified GO/KEGG terms affected by Mettl3-induced m6A modification. Protein-protein interaction analysis of proteins involved in these pathways highlighted GAPDH, ENO1, and TPI1 as three key hub genes. Conclusion: In MASLD, Mettl3 regulates the glycolytic pathway through m6A modification, influencing the occurrence and development of the disease via the key hub genes GAPDH, ENO1, and TPI1. These findings expand our understanding of MASLD and provide strong evidence for potential therapeutic targets and drug development.
2024-09-20 | PXD050565 | Pride
Project description:we find METTL3 associates with polyribosomes and promotes translation. METTL3 depletion inhibits translation, and both wild-type and catalytically inactive METTL3 promote translation when tethered to the 3' untranslated region (UTR) of a reporter mRNA. Mechanistically, METTL3 enhances mRNA translation through an interaction with the translation initiation machinery. m6A seq in A549 and H1299 cells, RNA seq in METTL3 knockdown cells
2016-07-03 | E-GEOD-76367 | biostudies-arrayexpress
Project description:Small-molecule Inhibition of METTL3 Suppresses Tumor Growth and Promotes Neuroblastoma Differentiation [meRIP-Seq]
| PRJNA1004271 | ENA