Reciprocal regulation of TWIST1 and OGT determines the decitabine efficacy in MDS/AML
Abstract Chemoresistance poses a significant impediment to effective treatment strategies for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Our previous study unveiled that oncogene TWIST1 interacted with DNA methyltransferase 3a (DNMT3a) to regulate the decitabine (DAC) resistan...
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-023-01278-y |
| _version_ | 1797557714623135744 |
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| author | Hongjiao Li Yi Wang Shuang Feng Kaijing Chang Xinwen Yu Fenfang Yang Haozhe Huang Yuanbo Wang Xiang Li Feng Guan |
| author_facet | Hongjiao Li Yi Wang Shuang Feng Kaijing Chang Xinwen Yu Fenfang Yang Haozhe Huang Yuanbo Wang Xiang Li Feng Guan |
| author_sort | Hongjiao Li |
| collection | DOAJ |
| description | Abstract Chemoresistance poses a significant impediment to effective treatment strategies for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Our previous study unveiled that oncogene TWIST1 interacted with DNA methyltransferase 3a (DNMT3a) to regulate the decitabine (DAC) resistance in MDS/AML. However, the underlying mechanism of TWIST1 dysregulation in DAC resistance remained enigmatic. Here, we found that O-GlcNAc modification was upregulated in CD34+ cells from MDS/AML patients who do not respond to DAC treatment. Functional study revealed that O-GlcNAcylation could stabilize TWIST1 by impeding its interaction with ubiquitin E3 ligase CBLC. In addition, as one typical transcription factor, TWIST1 could bind to the promoter of O-GlcNAc transferase (OGT) gene and activate its transcription. Collectively, we highlighted the crucial role of the O-GlcNAcylated TWIST1 in the chemoresistance capacity of MDS/AML clonal cells, which may pave the way for the development of a new therapeutic strategy targeting O-GlcNAcylated proteins and reducing the ratio of MDS/AML relapse. Video Abstract |
| first_indexed | 2024-03-10T17:20:16Z |
| format | Article |
| id | doaj.art-5a1b2ef9ca984599a29c15dd73d48436 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-03-10T17:20:16Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-5a1b2ef9ca984599a29c15dd73d484362023-11-20T10:22:06ZengBMCCell Communication and Signaling1478-811X2023-09-0121111210.1186/s12964-023-01278-yReciprocal regulation of TWIST1 and OGT determines the decitabine efficacy in MDS/AMLHongjiao Li0Yi Wang1Shuang Feng2Kaijing Chang3Xinwen Yu4Fenfang Yang5Haozhe Huang6Yuanbo Wang7Xiang Li8Feng Guan9Key Laboratory of Resource Biology and Biotechnology Western China, Ministry of Education; Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest UniversityDepartment of Hematology, Provincial People’s HospitalKey Laboratory of Resource Biology and Biotechnology Western China, Ministry of Education; Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest UniversityKey Laboratory of Resource Biology and Biotechnology Western China, Ministry of Education; Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest UniversityKey Laboratory of Resource Biology and Biotechnology Western China, Ministry of Education; Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest UniversityKey Laboratory of Resource Biology and Biotechnology Western China, Ministry of Education; Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest UniversityKey Laboratory of Resource Biology and Biotechnology Western China, Ministry of Education; Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest UniversityKey Laboratory of Resource Biology and Biotechnology Western China, Ministry of Education; Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest UniversityInstitute of Hematology, School of Medicine, Northwest UniversityKey Laboratory of Resource Biology and Biotechnology Western China, Ministry of Education; Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest UniversityAbstract Chemoresistance poses a significant impediment to effective treatment strategies for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Our previous study unveiled that oncogene TWIST1 interacted with DNA methyltransferase 3a (DNMT3a) to regulate the decitabine (DAC) resistance in MDS/AML. However, the underlying mechanism of TWIST1 dysregulation in DAC resistance remained enigmatic. Here, we found that O-GlcNAc modification was upregulated in CD34+ cells from MDS/AML patients who do not respond to DAC treatment. Functional study revealed that O-GlcNAcylation could stabilize TWIST1 by impeding its interaction with ubiquitin E3 ligase CBLC. In addition, as one typical transcription factor, TWIST1 could bind to the promoter of O-GlcNAc transferase (OGT) gene and activate its transcription. Collectively, we highlighted the crucial role of the O-GlcNAcylated TWIST1 in the chemoresistance capacity of MDS/AML clonal cells, which may pave the way for the development of a new therapeutic strategy targeting O-GlcNAcylated proteins and reducing the ratio of MDS/AML relapse. Video Abstracthttps://doi.org/10.1186/s12964-023-01278-yTWIST1OGTO-GlcNAcDAC resistanceMDS/AML |
| spellingShingle | Hongjiao Li Yi Wang Shuang Feng Kaijing Chang Xinwen Yu Fenfang Yang Haozhe Huang Yuanbo Wang Xiang Li Feng Guan Reciprocal regulation of TWIST1 and OGT determines the decitabine efficacy in MDS/AML Cell Communication and Signaling TWIST1 OGT O-GlcNAc DAC resistance MDS/AML |
| title | Reciprocal regulation of TWIST1 and OGT determines the decitabine efficacy in MDS/AML |
| title_full | Reciprocal regulation of TWIST1 and OGT determines the decitabine efficacy in MDS/AML |
| title_fullStr | Reciprocal regulation of TWIST1 and OGT determines the decitabine efficacy in MDS/AML |
| title_full_unstemmed | Reciprocal regulation of TWIST1 and OGT determines the decitabine efficacy in MDS/AML |
| title_short | Reciprocal regulation of TWIST1 and OGT determines the decitabine efficacy in MDS/AML |
| title_sort | reciprocal regulation of twist1 and ogt determines the decitabine efficacy in mds aml |
| topic | TWIST1 OGT O-GlcNAc DAC resistance MDS/AML |
| url | https://doi.org/10.1186/s12964-023-01278-y |
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