What question did this study set out to answer?

This research aims to understand how RNA methylation, specifically m6A, influences medulloblastoma growth and immune evasion.

April 5, 2026

Abstract 7880: Regulation of medulloblastoma growth and immune evasion by RNA methylation

Key Points

This research aims to understand how RNA methylation, specifically m6A, influences medulloblastoma growth and immune evasion.
Utilized genetically engineered mouse models and in vitro studies to assess METTL3's role.
Conducted RNA sequencing after METTL3 deletion to identify target genes.
Performed m6A profiling and pathway enrichment analysis on identified targets.
Tested pharmacological inhibition of m6A using STM9201 in multiple cell lines and mouse models.
Identified METTL3 as essential for tumor growth and immune evasion in medulloblastoma.
METTL3 target genes associated with immune and metabolic pathways were predominantly upregulated.
Pharmacological inhibition with STM9201 decreased m6A levels and cell viability in a dose-dependent manner.
Oral STM9201 administration significantly suppressed tumor growth in mouse models.

Abstract

Abstract Medulloblastoma (MB) is the most common malignant brain tumor in children. While advances in multimodal therapy have improved survival, many patients still succumb to the disease, and long-term survivors often experience debilitating neurological and developmental side effects. Post-transcriptional RNA modifications, collectively termed epitranscriptomics, have emerged as a critical regulator in cancer and development. N6 -methyladenosine (m6A) is the most prevalent eukaryotic RNA modification and regulates the stability and translation of modified mRNAs. The m6A methyltransferase, METTL3 promotes tumor growth and stemness in several cancers, yet its precise functions and therapeutic potential in MB remain poorly understood. Here, we investigated the role of RNA m6A modification in MB and identified METTL3 as an essential in vitro and in vivo dependency in genetically engineered mouse models of MB. RNAseq following METTL3 deletion revealed METTL3 target genes, the majority of which were upregulated. We further performed m6A profiling of MBs and overlapped it with RNAseq data to identify m6A dependent and downstream m6A independent targets of METTL3. Pathway enrichment analysis of METTL3 targets showed a strong enrichment for genes associated with innate immune response, antiviral response, RNA processing and cholesterol biosynthesis among others. In addition, METTL3 depletion enhanced the immunogenicity of MB tumors. Pharmacological inhibition of m6A by STM9201 in multiple MB cell lines decreased global mRNA m6A levels and the cell viability in a dose-dependent manner. Moreover, oral administration of STM9201 in MB mouse models suppressed tumor growth. Ongoing mechanistic studies aim to delineate the cell-intrinsic and cell-extrinsic pathways through which METTL3 regulates MB progression and immune response. Citation Format: Deobrat Dixit, Robert Wechsler-Reya. Regulation of medulloblastoma growth and immune evasion by RNA methylation abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7880.

Bookmark

Cite This Study

Dixit et al. (Fri,) studied this question.

synapsesocial.com/papers/69d1fd4ea79560c99a0a34a9 https://doi.org/https://doi.org/10.1158/1538-7445.am2026-7880

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

Bookmark