M2 macrophages-derived exosomal miR-3917 promotes the progression of lung cancer via targeting GRK6
Author:
Song Sinuo1, Zhao Yunping2, Wang Xiaoxing2, Tong Xinghe1, Chen Xiaobo2ORCID, Xiong Qiuxia3
Affiliation:
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
Abstract
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.
Funder
National Natural Science Foundation of China Kunming Medical University Applied Basic Research Joint Special Fund General Program
Publisher
Walter de Gruyter GmbH
Subject
Clinical Biochemistry,Molecular Biology,Biochemistry
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