EZH2 inhibition induces pyroptosis via RHA-mediated S100A9 overexpression in myelodysplastic syndromes
Abstract Myelodysplastic Syndromes (MDS) represent a group of heterogeneous myeloid clonal diseases derived from aberrant hematopoietic stem/progenitor cells. Enhancer of zeste homolog 2 (EZH2) is an important regulator in gene expression through methyltransferase-dependent or methyltransferase-inde...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Experimental Hematology & Oncology |
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| Online Access: | https://doi.org/10.1186/s40164-025-00600-3 |
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| author | Qi Zhang Yingwan Luo Li Ye Yuxia Wang Lu Wang Wenli Yang Wei Lang Shuanghong Zhu Lingxu Jiang Weimei Jin Chen Mei Xinping Zhou Yanling Ren Liya Ma Gaixiang Xu Bowatte Gedara Lakmal Vimukthi Bandara Bowattage Hongyan Tong Jie Sun |
| author_facet | Qi Zhang Yingwan Luo Li Ye Yuxia Wang Lu Wang Wenli Yang Wei Lang Shuanghong Zhu Lingxu Jiang Weimei Jin Chen Mei Xinping Zhou Yanling Ren Liya Ma Gaixiang Xu Bowatte Gedara Lakmal Vimukthi Bandara Bowattage Hongyan Tong Jie Sun |
| author_sort | Qi Zhang |
| collection | DOAJ |
| description | Abstract Myelodysplastic Syndromes (MDS) represent a group of heterogeneous myeloid clonal diseases derived from aberrant hematopoietic stem/progenitor cells. Enhancer of zeste homolog 2 (EZH2) is an important regulator in gene expression through methyltransferase-dependent or methyltransferase-independent mechanisms. Herein, we found EZH2 inhibition led to MDS cell pyroptosis through RNA Helicase A (RHA) down-regulation induced overexpression of S100A9, a key regulator of inflammasome activation and pyroptosis. Moreover, EZH2 inhibitor reduced tumor burden and prolonged the survival of the mice transplanted with MDS cells. In summary, our results uncovered a novel pyroptosis pathway induced by EZH2 inhibition and provided a rationale for EZH2 inhibitor treatment in MDS. |
| format | Article |
| id | doaj-art-6b7adac47b3440ce987f9991defac80f |
| institution | Kabale University |
| issn | 2162-3619 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Experimental Hematology & Oncology |
| spelling | doaj-art-6b7adac47b3440ce987f9991defac80f2025-02-02T12:12:00ZengBMCExperimental Hematology & Oncology2162-36192025-01-011411610.1186/s40164-025-00600-3EZH2 inhibition induces pyroptosis via RHA-mediated S100A9 overexpression in myelodysplastic syndromesQi Zhang0Yingwan Luo1Li Ye2Yuxia Wang3Lu Wang4Wenli Yang5Wei Lang6Shuanghong Zhu7Lingxu Jiang8Weimei Jin9Chen Mei10Xinping Zhou11Yanling Ren12Liya Ma13Gaixiang Xu14Bowatte Gedara Lakmal Vimukthi Bandara Bowattage15Hongyan Tong16Jie Sun17Department of Hematology, the First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Hematology, the First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Hematology, the First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Hematology, the First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Hematology, the First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Hematology, the First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Hematology, the First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Hematology, the First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Hematology, the First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Hematology, the First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Hematology, the First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Hematology, the First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Hematology, the First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Hematology, the First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Hematology, the First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Hematology, the First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Hematology, the First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Hematology, the First Affiliated Hospital, Zhejiang University School of MedicineAbstract Myelodysplastic Syndromes (MDS) represent a group of heterogeneous myeloid clonal diseases derived from aberrant hematopoietic stem/progenitor cells. Enhancer of zeste homolog 2 (EZH2) is an important regulator in gene expression through methyltransferase-dependent or methyltransferase-independent mechanisms. Herein, we found EZH2 inhibition led to MDS cell pyroptosis through RNA Helicase A (RHA) down-regulation induced overexpression of S100A9, a key regulator of inflammasome activation and pyroptosis. Moreover, EZH2 inhibitor reduced tumor burden and prolonged the survival of the mice transplanted with MDS cells. In summary, our results uncovered a novel pyroptosis pathway induced by EZH2 inhibition and provided a rationale for EZH2 inhibitor treatment in MDS.https://doi.org/10.1186/s40164-025-00600-3Myelodysplastic syndromesEnhancer of zeste homologue 2RNA helicase AS100 calcium binding protein A9Pyroptosis |
| spellingShingle | Qi Zhang Yingwan Luo Li Ye Yuxia Wang Lu Wang Wenli Yang Wei Lang Shuanghong Zhu Lingxu Jiang Weimei Jin Chen Mei Xinping Zhou Yanling Ren Liya Ma Gaixiang Xu Bowatte Gedara Lakmal Vimukthi Bandara Bowattage Hongyan Tong Jie Sun EZH2 inhibition induces pyroptosis via RHA-mediated S100A9 overexpression in myelodysplastic syndromes Experimental Hematology & Oncology Myelodysplastic syndromes Enhancer of zeste homologue 2 RNA helicase A S100 calcium binding protein A9 Pyroptosis |
| title | EZH2 inhibition induces pyroptosis via RHA-mediated S100A9 overexpression in myelodysplastic syndromes |
| title_full | EZH2 inhibition induces pyroptosis via RHA-mediated S100A9 overexpression in myelodysplastic syndromes |
| title_fullStr | EZH2 inhibition induces pyroptosis via RHA-mediated S100A9 overexpression in myelodysplastic syndromes |
| title_full_unstemmed | EZH2 inhibition induces pyroptosis via RHA-mediated S100A9 overexpression in myelodysplastic syndromes |
| title_short | EZH2 inhibition induces pyroptosis via RHA-mediated S100A9 overexpression in myelodysplastic syndromes |
| title_sort | ezh2 inhibition induces pyroptosis via rha mediated s100a9 overexpression in myelodysplastic syndromes |
| topic | Myelodysplastic syndromes Enhancer of zeste homologue 2 RNA helicase A S100 calcium binding protein A9 Pyroptosis |
| url | https://doi.org/10.1186/s40164-025-00600-3 |
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