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
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引用次数: 0
摘要
骨髓增生异常综合征（MDS）是一组源自异常造血干细胞/祖细胞的异质髓系克隆性疾病。zeste同源物2增强子（Enhancer of zeste homolog 2, EZH2）是一种重要的基因表达调控因子，通过甲基转移酶依赖或甲基转移酶不依赖的机制调控基因表达。本研究发现EZH2抑制通过RNA解旋酶A （RHA）下调诱导S100A9过表达导致MDS细胞焦亡，S100A9是炎性小体激活和焦亡的关键调节因子。此外，EZH2抑制剂降低了MDS细胞移植小鼠的肿瘤负荷，延长了小鼠的生存期。总之，我们的研究结果揭示了EZH2抑制诱导的一种新的焦亡途径，并为EZH2抑制剂治疗MDS提供了理论依据。
EZH2 inhibition induces pyroptosis via RHA-mediated S100A9 overexpression in myelodysplastic syndromes.
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.
期刊介绍：
Experimental Hematology & Oncology is an open access journal that encompasses all aspects of hematology and oncology with an emphasis on preclinical, basic, patient-oriented and translational research. The journal acts as an international platform for sharing laboratory findings in these areas and makes a deliberate effort to publish clinical trials with 'negative' results and basic science studies with provocative findings.
Experimental Hematology & Oncology publishes original work, hypothesis, commentaries and timely reviews. With open access and rapid turnaround time from submission to publication, the journal strives to be a hub for disseminating new knowledge and discussing controversial topics for both basic scientists and busy clinicians in the closely related fields of hematology and oncology.
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