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miR-106b-5p Inhibits IRF1/IFN-β Signaling to Promote M2 Macrophage Polarization of Glioblastoma

Authors Shi Y, Zhang B, Zhu J, Huang W, Han B, Wang Q, Qi C, Wang M, Liu F

Received 17 November 2019

Accepted for publication 6 July 2020

Published 30 July 2020 Volume 2020:13 Pages 7479—7492

DOI https://doi.org/10.2147/OTT.S238975

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Jianmin Xu


Yu Shi,1,* Bin Zhang,2,* Jian Zhu,3,* Wu Huang,4 Bin Han,4 Qilong Wang,4 Chunjian Qi,5 Minghai Wang,4 Fang Liu4

1Department of Neurology, Xuzhou Hospital Affiliated to Jiangsu University, Xuzhou, Jiangsu, People’s Republic of China; 2Department of Neurosurgery, Jintan People’s Hospital, Changzhou, Jiangsu, People’s Republic of China; 3Department of Neurosurgery, Yancheng No.1 People’s Hospital, Yancheng, Jiangsu, People’s Republic of China; 4Department of Neurosurgery, Nanjing Medical University Affiliated Changzhou NO.2 People’s Hospital, Changzhou, Jiangsu, People’s Republic of China; 5Department of Central Lab, Nanjing Medical University Affiliated Changzhou NO.2 People’s Hospital, Changzhou, Jiangsu, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Fang Liu
Department of Neurosurgery, Nanjing Medical University Affiliated Changzhou NO.2 People’s Hospital, Changzhou 213003, Jiangsu, People’s Republic of China
Email czdoctorliu@hotmail.com

Purpose: The microRNA (miRNA) profile changes in the tumor-associated macrophages. However, the role of miR-106b-5p in the glioblastoma-associated macrophages is poorly understood.
Materials and Methods: In our study, miR-106b-5p and M2 macrophage markers were detected by qRT-PCR and Western blotting in THP1 cells, with the conditioned medium from U251 cells or M2 macrophages in response to IL-4 stimulation and M1 macrophages stimulated by LPS and IFN-γ. IFN regulatory factor (IRF1) was identified as a target of miR-106b-5p in the glioma infiltrating macrophages by luciferase reporter assay. The molecular mechanisms involved in the miR-106b-5p-mediated regulation of M2 polarization were clarified by shRNA knockdown assay.
Results: Our results showed miR-106b-5p expression was upregulated in glioma-infiltrating macrophages. miR-106b-5p regulated M2 polarization of glioma infiltrating macrophages and enhanced the growth of glioma-infiltrating macrophages. IRF1 was identified as a target of miR-106b-5p. Furthermore, miR-106b-5p inhibited IRF1 expression by targeting IRF1/IFN-β pathway to promote M2 polarization of macrophages.
Conclusion: miR-106b-5p may inhibit IRF1/IFN-β signaling to promote M2 macrophage polarization of glioblastoma, and it may become a novel target for the treatment of glioblastoma.

Keywords: glioma, miR-106b-5p, IRF1/IFN-β, M2 macrophage polarization, glioma-associated microenvironment

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