MicroRNA-155 Regulates Inflammatory Cytokine Production in Tumor-associated Macrophages via Targeting C/EBPβ (original) (raw)

Cellular & Molecular Immunology volume 6, pages 343–352 (2009)Cite this article

Abstract

Macrophages (Mφ) are prominent components of solid tumors and exhibit distinct phenotypes in different microenvironments. We have recently found that tumors can alter the normal developmental process of Mφ to trigger transient activation of monocytes, but the underlying regulatory mechanisms are incompletely understood. Here, we showed that the protein expression of transcription factor C/EBPβ was markedly elevated in tumor-associated Mφ both in vitro and human tumors in situ. The expression of C/EBPβ protein correlated with cytokine production in tumor-activated monocytes. Moreover, we found that C/EBPβ expression was regulated at the post-transcriptional level and correlated with sustained reduction of microRNA-155 (miR-155) in tumor-activated monocytes. Bioinformatic analysis revealed that C/EBPβ is a potential target of miR-155 and luciferase assay confirmed that C/EBPβ translation is suppressed by miR-155 through interaction with the 3'UTR of C/EBPβ mRNA. Further analysis showed that induction of miR-155 suppressed C/EBPβ protein expression as well as cytokine production in tumor-activated monocytes, an effect which could be mimicked by silencing of C/EBPβ. These results indicate that tumor environment causes a sustained reduction of miR-155 in monocytes/Mφ, which in turn regulates the functional activities of monocytes/Mφ by releasing the translational inhibition of transcription factor C/EBPβ.

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Authors and Affiliations

  1. Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China
    Min He, Zhenqun Xu, Tong Ding, Dong-Ming Kuang & Limin Zheng

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  1. Min He
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  2. Zhenqun Xu
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  3. Tong Ding
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  4. Dong-Ming Kuang
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  5. Limin Zheng
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Correspondence toLimin Zheng.

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He, M., Xu, Z., Ding, T. et al. MicroRNA-155 Regulates Inflammatory Cytokine Production in Tumor-associated Macrophages via Targeting C/EBPβ.Cell Mol Immunol 6, 343–352 (2009). https://doi.org/10.1038/cmi.2009.45

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