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外泌体 miR-486 通过靶向 Sirt1 调节缺氧诱导的红白血病细胞红系分化。

Exosomal miR-486 regulates hypoxia-induced erythroid differentiation of erythroleukemia cells through targeting Sirt1.

作者信息

Shi Xue-Feng, Wang Hua, Kong Fan-Xuan, Xu Qin-Qin, Xiao Feng-Jun, Yang Yue-Feng, Ge Ri-Li, Wang Li-Sheng

机构信息

High Altitude Medicine of Ministry of Chinese Education and Research Center for High Altitude Medicine, Qinghai University, Xining 810001, PR China; Qinghai Provincial People's Hospital, Xining 810007, PR China.

Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China; Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.

出版信息

Exp Cell Res. 2017 Feb 1;351(1):74-81. doi: 10.1016/j.yexcr.2016.12.023. Epub 2016 Dec 30.

DOI:10.1016/j.yexcr.2016.12.023
PMID:28043832
Abstract

MicroRNAs (miRNAs) regulate the hypoxia-induced erythroid differentiation of hematopoietic cells. In this study, we identified that miR-486 was a rapid response miRNA to hypoxia in erythroleukemia TF-1 cells. Hypoxia exposure increased both intracellular and miR-486 levels of TF-1 cells. Ectopic miR-486 expression enhanced the growth and erythroid differentiation of TF-1 cells, whereas miR-486 inhibition suppressed their growth and erythroid differentiation. Treatment of TF-1 and cord blood CD34+ cells with exogenous containing miR-486 resulted in an increase of intracellular miR-486 level and enhanced erythroid differentiation. Furthermore, we identified that Sirt1 is a miR-486 target gene which modulates hypoxia-induced erythroid differentiation of TF-1 cells. Thus we identified a novel miRNA regulatory network that contributes to hypoxia-induced erythroid differentiation of hematopoietic cells.

摘要

微小RNA(miRNA)可调节造血细胞的缺氧诱导红系分化。在本研究中,我们鉴定出miR-486是红白血病TF-1细胞中对缺氧的快速反应miRNA。缺氧暴露增加了TF-1细胞的细胞内miR-486水平。异位表达miR-486可增强TF-1细胞的生长和红系分化,而抑制miR-486则会抑制其生长和红系分化。用含miR-486的外源性物质处理TF-1细胞和脐带血CD34+细胞,导致细胞内miR-486水平升高并增强了红系分化。此外,我们鉴定出Sirt1是一个miR-486靶基因,其可调节TF-1细胞的缺氧诱导红系分化。因此,我们鉴定出了一个新的miRNA调控网络,该网络有助于造血细胞的缺氧诱导红系分化。

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