LncRNA-MM2P Identified as a Modulator of Macrophage M2 Polarization

M2 polarization of macrophages is essential for their function in immunologic tolerance, which might promote tumorigenesis. However, the molecular mechanism behind the polarization process is not fully understood. Given that several lines of evidence have suggested that long noncoding RNAs (lncRNAs)...

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Published in:Cancer immunology research 2019-02, Vol.7 (2), p.292-305
Main Authors: Cao, Ji, Dong, Rong, Jiang, Li, Gong, Yanling, Yuan, Meng, You, Jieqiong, Meng, Wen, Chen, Zhanlei, Zhang, Ning, Weng, Qinjie, Zhu, Hong, He, Qiaojun, Ying, Meidan, Yang, Bo
Format: Article
Language:English
Subjects:
Animals
Cell Line, Tumor
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - metabolism
Computational Biology - methods
Gene Expression Profiling
Humans
Interleukins - metabolism
Macrophage Activation - genetics
Macrophage Activation - immunology
Macrophages - immunology
Macrophages - metabolism
Mice
Neovascularization, Physiologic - genetics
Phosphorylation
RAW 264.7 Cells
RNA, Long Noncoding - genetics
STAT6 Transcription Factor - metabolism
Transcriptome
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Summary:M2 polarization of macrophages is essential for their function in immunologic tolerance, which might promote tumorigenesis. However, the molecular mechanism behind the polarization process is not fully understood. Given that several lines of evidence have suggested that long noncoding RNAs (lncRNAs) could be involved in regulating immune cell differentiation and function, the current study aimed to identify the lncRNAs that specifically modulate M2 macrophage polarization. By utilizing a series of cell-based M2 macrophage polarization models, a total of 25 lncRNAs with altered expression were documented based on lncRNA microarray-based profiling assays. Among them, lncRNA-MM2P was the only lncRNA upregulated during M2 polarization but downregulated in M1 macrophages. Knockdown of lncRNA-MM2P blocked cytokine-driven M2 polarization of macrophages and weakened the angiogenesis-promoting feature of M2 macrophages by reducing phosphorylation on STAT6. Moreover, manipulating lncRNA-MM2P in macrophages impaired macrophage-mediated promotion of tumorigenesis, tumor growth and tumor angiogenesis. Collectively, our study identifies lncRNA-MM2P as a modulator required for macrophage M2 polarization and uncovers its role in macrophage-promoted tumorigenesis.
ISSN:2326-6066
2326-6074
DOI:10.1158/2326-6066.CIR-18-0145