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Small-molecule Inhibition of METTL3 Suppresses Tumor Growth and Promotes Neuroblastoma Differentiation

ABSTRACT: Small-molecule Inhibition of METTL3 Suppresses Tumor Growth and Promotes Neuroblastoma Differentiation

PROVIDER: PRJNA1004276 | ENA |

REPOSITORIES: ENA

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Small-molecule Inhibition of METTL3 Suppresses Tumor Growth and Promotes Neuroblastoma Differentiation [meRIP-Seq]

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

Small-molecule Inhibition of METTL3 Suppresses Tumor Growth and Promotes Neuroblastoma Differentiation [RNA-Seq Decay]

2024-04-10 | GSE240581 | GEO

Small-molecule Inhibition of METTL3 Suppresses Tumor Growth and Promotes Neuroblastoma Differentiation [RNA-Seq STM]

2024-04-10 | GSE262731 | GEO

Small-molecule Inhibition of METTL3 Suppresses Tumor Growth and Promotes Neuroblastoma Differentiation [RNA-seq siMETTL3]

2024-04-10 | GSE263118 | GEO

Small-molecule Inhibition of METTL3 Suppresses Tumor Growth and Promotes Neuroblastoma Differentiation [meRIP-Seq]

Project description:Small-molecule Inhibition of METTL3 Suppresses Tumor Growth and Promotes Neuroblastoma Differentiation [meRIP-Seq]

| PRJNA1004271 | ENA

Small-molecule Inhibition of METTL3 Suppresses Tumor Growth and Promotes Neuroblastoma Differentiation [RNA-Seq Decay]

Project description:Small-molecule Inhibition of METTL3 Suppresses Tumor Growth and Promotes Neuroblastoma Differentiation [RNA-Seq Decay]

| PRJNA1004269 | ENA

Small-molecule Inhibition of METTL3 Suppresses Tumor Growth and Promotes Neuroblastoma Differentiation [RNA-Seq STM]

Project description:Small-molecule Inhibition of METTL3 Suppresses Tumor Growth and Promotes Neuroblastoma Differentiation [RNA-Seq STM]

| PRJNA1093074 | ENA

Small-molecule Inhibition of METTL3 Suppresses Tumor Growth and Promotes Neuroblastoma Differentiation [RNA-seq siMETTL3]

Project description:Small-molecule Inhibition of METTL3 Suppresses Tumor Growth and Promotes Neuroblastoma Differentiation [RNA-seq siMETTL3]

| PRJNA1095886 | ENA

Small-molecule Inhibition of METTL3 Suppresses Tumor Growth and Promotes Neuroblastoma Differentiation

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-04-10 | GSE240595 | GEO

The impact of small molecule inhibition of METTL3 on normal haematopoiesis

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

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