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Publication : MicroRNA 34a promotes ionizing radiation-induced DNA damage repair in murine hematopoietic stem cells.

First Author  Zeng H Year  2019
Journal  FASEB J Volume  33
Issue  7 Pages  8138-8147
PubMed ID  30922079 Mgi Jnum  J:290885
Mgi Id  MGI:6442364 Doi  10.1096/fj.201802639R
Citation  Zeng H, et al. (2019) MicroRNA 34a promotes ionizing radiation-induced DNA damage repair in murine hematopoietic stem cells. FASEB J 33(7):8138-8147
abstractText  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.
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