Abstract
Sirtuin 1 (SIRT1) is a protein deacetylase, which regulates various physiological activities by deacetylating different protein substrates. An increasing number of studies have revealed critical roles of SIRT1 in different aspects of cancers including metabolism, proliferation, genomic instability, and chemotherapy resistance. Depending on the protein targets in a certain oncogenic context, SIRT1 may play a unique role in each individual blood cancer subtype. Our previous work showed that activation of SIRT1 in primitive leukemia cells of acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML) promotes disease maintenance. On the other hand, an SIRT1 agonist was shown to disrupt maintenance of myelodysplastic syndrome (MDS) stem cells and holds promise as a potential therapeutic approach. Herein, we present a concise summary of the different functions of SIRT1 in hematologic malignancies.
概 要
SIRT1 属于烟酰胺腺嘌呤二核苷酸 (NAD) 依赖的组蛋白脱乙酰酶家族成员。 通过对不同蛋白底物去乙酰化, SIRT1 参与了细胞代谢、 细胞周期以及 DNA 修复等多种生理过程的调控。 许多研究表明: SIRT1 在肿瘤中的功能具有两面性, 在急性髓系白血病和慢性粒细胞白血病中 SIRT1 的高表达促进了疾病的进展; 而在骨髓增生异常综合征中, SIRT1 的活化却能抑制肿瘤干细胞。 本综述回顾了 SIRT1 在血液系统肿瘤中的研究进展, 总结了不同肿瘤类型中 SIRT1 的表达水平以及相应的调控机制, 并探讨了潜在的治疗靶点和应用前景。
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We thank Marjorie ROBBINS (Beckman Research Institute, City of Hope Medical Center, Duarte, USA) for critical reading of the manuscript.
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Project supported by the National Institutes of Health (No. R01HL141336), the Margaret E. Early Medical Research Trust Award, the Stop Cancer Research Career Development Award, V Scholar Award of Cancer Research, and the Gehr Family Center for Leukemia Research, USA
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Huang, Ft., Sun, J., Zhang, L. et al. Role of SIRT1 in hematologic malignancies. J. Zhejiang Univ. Sci. B 20, 391–398 (2019). https://doi.org/10.1631/jzus.B1900148
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DOI: https://doi.org/10.1631/jzus.B1900148