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BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

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

Authors: Zhenbiao Xu, Lianmei Zhao, Xin Yang, Sisi Ma, Yehua Ge, Yanxin Liu, Shilian Liu, Juan Shi, Dexian Zheng

Published in: BMC Cancer | Issue 1/2016

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Abstract

Background

MicroRNAs 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.

Methods

Luciferase 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.

Results

Here, 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.

Conclusions

These data suggest that mmu-miR-125b decreases NO production in activated macrophages at least partially by suppressing eEF2K and CCNA2 expression.
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Metadata
Title
Mmu-miR-125b overexpression suppresses NO production in activated macrophages by targeting eEF2K and CCNA2
Authors
Zhenbiao Xu
Lianmei Zhao
Xin Yang
Sisi Ma
Yehua Ge
Yanxin Liu
Shilian Liu
Juan Shi
Dexian Zheng
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2288-z

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