Mmu-miR-125b overexpression suppresses NO production in activated macrophages by targeting eEF2K and CCNA2

BMC Cancer

Research Article

Lianmei Zhao¹  Yehua Ge¹  Dexian Zheng¹  Juan Shi¹  Xin Yang¹  Shilian Liu¹  Zhenbiao Xu¹  Sisi Ma¹  Yanxin Liu¹ 

[1]State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, 100005, Beijing, China

关键词: Mmu-miR-125;    Macrophages;    Nitric oxide;    eEF2K;    CCNA2;   

DOI  :  10.1186/s12885-016-2288-z

 received in 2015-05-26, accepted in 2016-03-22,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundMicroRNAs have been shown to be important regulators of the immune response and the development of the immune system. It was reported that microRNA-125b (miR-125b) was down-regulated in macrophages challenged with endotoxin. However, little is known about the function and mechanism of action of miR-125b in macrophage activation. Macrophages use L-arginine to synthesize nitric oxide (NO) through inducible NO synthase (iNOS), and the released NO contributes to the tumoricidal activity of macrophages.MethodsLuciferase reporter assays were employed to validate regulation of a putative target of miR-125b. The effect of miR-125b on endogenous levels of this target were subsequently confirmed via Western blot. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to determine the expression level of miR-125b in macrophage. MTS assays were conducted to explore the impact of miR-125b overexpression on the cell viability of 4T1 cells.ResultsHere, we demonstrate that mmu-miR-125b overexpression suppresses NO production in activated macrophages and that LPS-activated macrophages with overexpressed mmu-miR-125b promote 4T1 tumor cell proliferation in vitro and 4T1 tumor growth in vivo. CCNA2 and eEF2K are the direct and functional targets of mmu-miR-125b in macrophages; CCNA2 and eEF2K expression was knocked down, which mimicked the mmu-miR-125b overexpression phenotype.ConclusionsThese data suggest that mmu-miR-125b decreases NO production in activated macrophages at least partially by suppressing eEF2K and CCNA2 expression.

【 授权许可】

CC BY   
© Xu et al. 2016