O-GlcNAcylated FTO promotes m6A modification of SOX4 to enhance MDS/AML cell proliferation
Abstract 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-Gl...
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BMC
2025-01-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-025-02058-6 |
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| author | Junjie Gou Jingjing Bi Kexin Wang Lei Lei Yanli Feng Zengqi Tan Jiaojiao Gao Yanan Song Enci Kang Feng Guan Xiang Li |
| author_facet | Junjie Gou Jingjing Bi Kexin Wang Lei Lei Yanli Feng Zengqi Tan Jiaojiao Gao Yanan Song Enci Kang Feng Guan Xiang Li |
| author_sort | Junjie Gou |
| collection | DOAJ |
| description | Abstract 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 an m6A-dependent manner, resulting in increased AKT and MAPK phosphorylation and decreased cell apoptosis. Inhibiting FTO O-GlcNAcylation significantly slowed AML progression in vitro, a finding supported by clinical data in MDS/AML patients. In conclusion, our study highlights the crucial role of FTO O-GlcNAcylation in RNA m6A methylation and the progression of MDS/AML, thereby providing a potential therapeutic avenue for these formidable diseases. |
| format | Article |
| id | doaj-art-a01293ff3b5f4c549dc0de74dae34b99 |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Cell Communication and Signaling |
| spelling | doaj-art-a01293ff3b5f4c549dc0de74dae34b992025-01-26T12:44:48ZengBMCCell Communication and Signaling1478-811X2025-01-0123111310.1186/s12964-025-02058-6O-GlcNAcylated FTO promotes m6A modification of SOX4 to enhance MDS/AML cell proliferationJunjie Gou0Jingjing Bi1Kexin Wang2Lei Lei3Yanli Feng4Zengqi Tan5Jiaojiao Gao6Yanan Song7Enci Kang8Feng Guan9Xiang Li10Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest UniversityKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest UniversityKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest UniversityKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest UniversityDepartment of Hematology, Provincial People’s HospitalInstitute of Hematology, School of Medicine, Northwest UniversityKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest UniversityKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest UniversityXi’an Gaoxin No.1 High SchoolKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest UniversityKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest UniversityAbstract 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 an m6A-dependent manner, resulting in increased AKT and MAPK phosphorylation and decreased cell apoptosis. Inhibiting FTO O-GlcNAcylation significantly slowed AML progression in vitro, a finding supported by clinical data in MDS/AML patients. In conclusion, our study highlights the crucial role of FTO O-GlcNAcylation in RNA m6A methylation and the progression of MDS/AML, thereby providing a potential therapeutic avenue for these formidable diseases.https://doi.org/10.1186/s12964-025-02058-6Myelodysplastic syndromes (MDS)Acute myeloid leukemia (AML)O-linked N-acetyglucosamine (O-GlcNAc)Fat mass and obesity-associated protein (FTO)SRY related high mobility group box (SOX4) |
| spellingShingle | Junjie Gou Jingjing Bi Kexin Wang Lei Lei Yanli Feng Zengqi Tan Jiaojiao Gao Yanan Song Enci Kang Feng Guan Xiang Li O-GlcNAcylated FTO promotes m6A modification of SOX4 to enhance MDS/AML cell proliferation Cell Communication and Signaling Myelodysplastic syndromes (MDS) Acute myeloid leukemia (AML) O-linked N-acetyglucosamine (O-GlcNAc) Fat mass and obesity-associated protein (FTO) SRY related high mobility group box (SOX4) |
| title | O-GlcNAcylated FTO promotes m6A modification of SOX4 to enhance MDS/AML cell proliferation |
| title_full | O-GlcNAcylated FTO promotes m6A modification of SOX4 to enhance MDS/AML cell proliferation |
| title_fullStr | O-GlcNAcylated FTO promotes m6A modification of SOX4 to enhance MDS/AML cell proliferation |
| title_full_unstemmed | O-GlcNAcylated FTO promotes m6A modification of SOX4 to enhance MDS/AML cell proliferation |
| title_short | O-GlcNAcylated FTO promotes m6A modification of SOX4 to enhance MDS/AML cell proliferation |
| title_sort | o glcnacylated fto promotes m6a modification of sox4 to enhance mds aml cell proliferation |
| topic | Myelodysplastic syndromes (MDS) Acute myeloid leukemia (AML) O-linked N-acetyglucosamine (O-GlcNAc) Fat mass and obesity-associated protein (FTO) SRY related high mobility group box (SOX4) |
| url | https://doi.org/10.1186/s12964-025-02058-6 |
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