MicroRNA 34a promotes ionizing radiation–induced DNA damage repair in murine hematopoietic stem cells
MicroRNA 34a promotes ionizing radiation–induced DNA damage repair in murine hematopoietic stem cells
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DOI：
10.1096/fj.201802639r
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发表时间：
2019-03
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影响因子：
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通讯作者：
Haotao Zeng;Mengjia Hu;Yukai Lu;Zihao Zhang;Yang Xu;Song Wang;Mo Chen;M. Shen;Cheng Wang-Cheng-Wa
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文献类型：
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作者：
Haotao Zeng;Mengjia Hu;Yukai Lu;Zihao Zhang;Yang Xu;Song Wang;Mo Chen;M. Shen;Cheng Wang-Cheng-Wa
造血干细胞（HSCs）是造血系统的重要组成部分，维持着造血功能。先前的研究已经报道了microRNA（miRNAs）在调控HSC自我更新和分化中的重要性。在这项研究中，我们发现miRNA 34 a（miR-34 a）的表达在电离辐射（IR）小鼠的HSC中显著上调。在辐射诱导的miR-34 a缺陷小鼠的HSC中观察到数量减少和DNA损伤修复以及凋亡增加，尽管miR-34 a对稳态造血作用不利。进一步的研究表明，miR-34 a缺陷的HSC表现出参与同源重组和非同源末端连接的DNA修复相关基因的表达降低。竞争性移植证实，miR-34 a的缺失导致辐射暴露后HSC的长期造血功能更严重的损害。因此，用miR-34 a agomir治疗小鼠可以显著减轻HSC中辐射诱导的DNA损伤。我们的研究结果表明，miR-34 a有助于促进照射后HSC的存活，这为保护HSC免受IR提供了一种有前途的方法。曾，H.，胡，M.，吕，Y.，张志，徐，Y.，王，S.，陈美，沈，M.，Wang，C.，中国地质大学，Chen，F.，Du，C.，唐，Y.，苏，Y.，陈淑仪，Wang，J. MicroRNA 34 a促进小鼠造血干细胞中电离辐射诱导的DNA损伤修复。FASEB J. 33，8138-8147（2019）。www.fasebj.org
Hematopoietic stem cells (HSCs) establish the entire hematopoietic system and maintain lifelong hematopoiesis. Previous studies have reported the significance of microRNAs (miRNAs) in the regulation of self‐renewal and differentiation of HSCs. In this study, we show that the expression of miRNA 34a (miR‐34a) is markedly up‐regulated in HSCs from mice subjected to ionizing radiation (IR). Reduced numbers and DNA damage repair, as well as increased apoptosis, are observed in HSCs from miR‐34a–deficient mice induced by irradiation, although miR‐34a is dispensable for steady‐state hematopoiesis. Further investigations show that HSCs deficient in miR‐34a exhibit decreased expressions of DNA repair–associated genes involved in homologous recombination and nonhomologous end joining. Competitive transplantation confirms that loss of miR‐34a leads to more severe impairment of the long‐term hematopoietic function of HSCs after irradiation exposure. Consistently, treating mice with an miR‐34a agomir can significantly alleviate irradiation‐induced DNA damage in HSCs. Our findings demonstrate that miR‐34a contributes to promoting HSCs' survival after irradiation, which provides a promising approach for protecting HSCs from IR.—Zeng, H., Hu, M., Lu, Y., Zhang, Z., Xu, Y., Wang, S., Chen, M., Shen, M., Wang, C., Chen, F., Du, C., Tang, Y., Su, Y., Chen, S., Wang, J. MicroRNA 34a promotes ionizing radiation–induced DNA damage repair in murine hematopoietic stem cells. FASEB J. 33, 8138–8147 (2019). www.fasebj.org