biostudies-literatureGou JYoung Scholars of Shaanxi Provincethe Natural Science Foundation of Shaanxi Provincethe National Science Foundation of ChinaShaanxi Innovation Team Project43https://www.ebi.ac.uk/biostudies/studies/S-EPMC11761745biostudies-literatureUnknown23(1)Fat mass and obesity-associated protein (FTO) was the first m6A demethylase identified, which is responsible for eliminating m6A modifications in target RNAs. While it is well-established that numerous cytosolic and nuclear proteins undergo O-GlcNAcylation, the possibility of FTO being O-GlcNAcylated and its functional implications remain unclear. This study found that a negative correlation between FTO expression and O-GlcNAcylation in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The decreased O-GlcNAcylation on FTO can result in diminished m6A modification of SRY-related high mobility group box 4 (SOX4). This led to the promotion of cell apoptosis and inhibition of cell proliferation in MDS/AML. The O-GlcNAcylation of FTO stabilized SOX4 transcripts in aCell communication and signaling : CCSO-GlcNAcylated FTO promotes m6A modification of SOX4 to enhance MDS/AML cell proliferation.PMC11761745(2021SF-294)(2023-CX-TD-58)No. 32071274(2021JC-39)No. 82370147Kang ELi XLei LTan ZFeng YGuan FGao JGou JBi JWang KSong YfalseO-GlcNAcylated FTO promotes m6A modification of SOX4 to enhance MDS/AML cell proliferation.Fat mass and obesity-associated protein (FTO) was the first m6A demethylase identified, which is responsible for eliminating m6A modifications in target RNAs. While it is well-established that numerous cytosolic and nuclear proteins undergo O-GlcNAcylation, the possibility of FTO being O-GlcNAcylated and its functional implications remain unclear. This study found that a negative correlation between FTO expression and O-GlcNAcylation in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The decreased O-GlcNAcylation on FTO can result in diminished m6A modification of SRY-related high mobility group box 4 (SOX4). This led to the promotion of cell apoptosis and inhibition of cell proliferation in MDS/AML. The O-GlcNAcylation of FTO stabilized SOX4 transcripts in a2025-01-01T00:00:00Z2025 Jan2025-04-18T14:28:01.817Z2025-04-07T00:39:34.324ZS-EPMC117617453984946110.1186/s12964-025-02058-6