M2 macrophages-derived exosomal miR-3917 promotes the progression of lung cancer via targeting GRK6

Sinuo Song; Yunping Zhao; Xiaoxing Wang; Xinghe Tong; Xiaobo Chen; Qiuxia Xiong

doi:10.1515/hsz-2022-0162

Article

M2 macrophages-derived exosomal miR-3917 promotes the progression of lung cancer via targeting GRK6

Sinuo Song , Yunping Zhao , Xiaoxing Wang , Xinghe Tong , Xiaobo Chen and Qiuxia Xiong

Published/Copyright: October 20, 2022

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From the journal Biological Chemistry Volume 404 Issue 1

Abstract

Macrophages in the tumor microenvironment (TME) can serve as potential targets for therapeutic intervention. The aim of this study was to investigate the molecular mechanism by which M2 macrophage-derived exosomes (M2-Ex) affect lung cancer progression through miRNA transport. The THP-1 cells were differentiated into M0 and M2 macrophages. M2-Ex were isolated and identified by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Cancer tissues and adjacent tissues of non-small-cell lung cancer (NSCLC) patients were collected. H1299 and A549 cells were co-cultured with M2-Ex. Subcutaneous xenograft mouse model was established. miR-3917 is highly expressed in lung cancer tissues and M2-Ex. Interference of miR-3917 in M2-Ex inhibits H1299 cell proliferation, migration and invasion, while overexpression of miR-3917 had the opposite effect in A549 cells. M2-Ex promote tumor growth by delivering miR-3917 in vivo. miR-3917 could target G protein-coupled receptor kinase 6 (GRK6), and interference of miR-3917 in M2-Ex inhibits H1299 cells proliferation, migration and invasion by up-regulating GRK6 level, while overexpression of miR-3917 had the opposite effect in A549 cells. M2-Ex can transfer miR-3917 into lung cancer cells and promote lung cancer progression, providing theoretical basis for the diagnosis and effective treatment of lung cancer.

Keywords: exosomes; GRK6; lung cancer; M2 macrophages; miR-3917

Corresponding author: Xiaobo Chen, Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Rd., Kunming 650332, China, E-mail: xiaobo_chen@yeah.net

Funding source: National Natural Science Foundation of China

Award Identifier / Grant number: No. 82060515

Funding source: Kunming Medical University Applied Basic Research Joint Special Fund General Program

Award Identifier / Grant number: No. 202001AY070001-025

Author contributions: Participated in research design: Sinuo Song. Conducted experiments: XX. Methodology: Sinuo Song, Yunping Zhao, Xiaoxing Wang. Performed data analysis: Sinuo Song, Xinghe Tong, Qiuxia Xiong. Wrote or contributed to the writing of the manuscript: Sinuo Song, Xiaobo Chen. All authors have read and agreed to the published version of the manuscript.
Research funding: This study was supported by National Natural Science Foundation of China (No. 82060515) and Kunming Medical University Applied Basic Research Joint Special Fund General Program (No. 202001AY070001-025).
Conflict of interest statement: None.

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Received: 2022-04-15

Accepted: 2022-08-24

Published Online: 2022-10-20

Published in Print: 2023-01-27

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Articles in the same Issue

https://doi.org/10.1515/hsz-2022-0162

Keywords for this article

exosomes; GRK6; lung cancer; M2 macrophages; miR-3917