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

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

Biol Chem. 2022 Oct 20;404(1):41-57. doi: 10.1515/hsz-2022-0162. Print 2023 Jan 27.

Authors

Sinuo Song¹, Yunping Zhao², Xiaoxing Wang², Xinghe Tong¹, Xiaobo Chen², Qiuxia Xiong³

Affiliations

¹ Department of Medical Management, 920th Hospital of Joint Logistics Support Force; Kunming 650032, China.
² Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Rd., Kunming 650332, China.
³ Department of Clinical Laboratory, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China.

PMID: 36261031
DOI: 10.1515/hsz-2022-0162

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

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carcinoma, Non-Small-Cell Lung* / genetics
Carcinoma, Non-Small-Cell Lung* / pathology
Cell Line, Tumor
Cell Proliferation
Exosomes* / genetics
Humans
Lung Neoplasms* / genetics
Lung Neoplasms* / pathology
Macrophages
Mice
MicroRNAs* / genetics
Tumor Microenvironment

Substances

MicroRNAs