PXD058793-1

PXD058793 is an original dataset announced via ProteomeXchange.

Title	RNA N6-Methyladenosine (m6A) regulates cell cycle progression in Diffuse Midline Glioma (DMG) and confers sensitivity to FTO inhibition
Description	Diffuse Midline Gliomas (DMG) are deadly pediatric brain cancers with limited treatment options. These tumors likely arise from oligodendrocyte precursor cells (OPC) that acquire a driver histone mutation, leading to an aberrant epigenome. RNA N6-methyladenosine (m6A) is a vital epi-transcriptomic modification that regulates RNA processes and plays a significant role in OPC development through its regulation of transcripts involved in histone modification processes. Despite this pivotal role in OPC biology, the epi-transcriptome has not yet been investigated in DMG, and its interrogation may uncover new therapeutic options and improve our understanding of this disease. Therefore, for the first time, we generated base-resolution m6A landscapes for patient-derived DMG cultures and revealed a critical role in cell cycle regulation. We also find that DMG is sensitive to the inhibition of the m6A demethylase Fat Mass and Obesity Associated (FTO), with this inhibition leading to decreased survival and S-phase arrest/stress. Additionally, key cell cycle regulators, such as PLK1, are m6A-modified, contain YTHDF2 binding sites, and show significant changes following FTO inhibition on transcriptomic and proteomic levels. Collectively, these findings highlight the epi-transcriptome and its regulators as promising therapeutic targets for this currently uncurable disease.
HostingRepository	PRIDE
AnnounceDate	2026-03-23
AnnouncementXML	Submission_2026-03-22_20:26:24.386.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Samuel Ross
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	Orbitrap Fusion Lumos; Q TRAP

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-11 19:57:21	ID requested
⏵ 1	2026-03-22 20:26:24	announced

Dataset with its publication pending

submitter keyword: None

Marcel E.
contact affiliation	The University of Sydney
contact email	Marcel.dinger@sydney.edu.au
lab head
Samuel Ross
contact affiliation	The University of Sydney
contact email	samuel.ross@sydney.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD058793
     1. Label: PRIDE project
     2. Name: RNA N6-Methyladenosine (m6A) regulates cell cycle progression in Diffuse Midline Glioma (DMG) and confers sensitivity to FTO inhibition