miR-181a Induces Macrophage Polarized to M2 Phenotype and Promotes M2 Macrophage-mediated Tumor Cell Metastasis by Targeting KLF6 and C/EBPα.
Macrophages can acquire a variety of polarization status and functions: classically activated macrophages (M1 macrophages); alternatively activated macrophages (M2 macrophages). However, the molecular basis of the process is still unclear. Here, this study addresses that microRNA-181a (miR-181a) is a key molecule controlling macrophage polarization. We found that miR-181a is overexpressed in M2 macrophages than in M1 macrophages. miR-181a expression was decreased when M2 phenotype converted to M1, whereas it increased when M1 phenotype converted to M2. Overexpression of miR-181a in M1 macrophages diminished M1 phenotype expression while promoting polarization to the M2 phenotype. In contrast, knockdown of miR-181a in M2 macrophages promoted M1 polarization and diminished M2 phenotype expression. Mechanistically, Bioinformatic analysis revealed that Kruppel-like factor 6 (KLF6) and CCAAT/enhancer binding protein-α (C/EBPα) is a potential target of miR-181a and luciferase assay confirmed that KLF6 and C/EBPα translation is suppressed by miR-181a through interaction with the 3'UTR of KLF6 and C/EBPα mRNA. Further analysis showed that induction of miR-181a suppressed KLF6 and C/EBPα protein expression. Importantly, miR-181a also diminishes M2 macrophages-mediated migration and invasion capacity of tumor cells. Collectively, our results suggest that miR-181a plays a significant role in regulating macrophage polarization through directly target KLF6 and C/EBPα.
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.
Jia
J
Bi
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.
Xianxin
X
Zeng
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.
Lin
L
Zhao
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.
Qian
Q
Wei
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.
Lifeng
L
Yu
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.
Xinnan
X
Wang
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.
Zhaojin
Z
Yu
Department of Immunology, School of Basic Medical Science, China Medical university, Shenyang, Liaoning, China.
Yaming
Y
Cao
Department of Immunology, School of Basic Medical Science, China Medical university, Shenyang, Liaoning, China.
Fengping
F
Shan
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.
Minjie
M
Wei
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