Статья

Tumor cell-derived exosomal microRNA-146a promotes non-small cell lung cancer cell invasion and proliferation by inhibiting M1 macrophage polarization

Zhi YanDepartment of Laboratory Medicine, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, ChinaJianxun WenDepartment of Medical Experiment Center, the Basic Medical Sciences College of Inner Mongolia Medical University, Hohhot, ChinaXi‐Shan CaoDepartment of Laboratory Medicine, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, ChinaWen ZhaoDepartment of Laboratory Medicine, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, ChinaYuling HanDepartment of Laboratory Medicine, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, ChinaXuhui WenDepartment of Laboratory Medicine, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, ChinaYan LiDepartment of Respiratory and Critical Care Medicine, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, ChinaMan ZhangDepartment of Thoracic Surgery, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, ChinaYafei WangDepartment of Laboratory Medicine, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, ChinaLing HaiDepartment of Pathology, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, ChinaYingjun WangDepartment of Laboratory Medicine, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, ChinaWen‐Qi ZhengDepartment of Laboratory Medicine, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, ChinaZhide HuDepartment of Laboratory Medicine, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China

2022en

ABI

Аннотация

Background: Tumor-associated macrophages (TAMs) affects the outcomes of non-small cell lung cancer (NSCLC). NSCLC cells released exosomes to suppress the antitumor activity of TAMs. MiR-146a is a critical regulator in TAM polarization. We hypothesized that NSCLC cells released exosomal miR-146a to regulate TAM polarization and thus affected its antitumor activity. Methods: We used H1299 cells-derived exosomes to stimulate THP-1 cells that was pretreated with phorbol 12-myristate 13-acetate (M0 macrophage). Flow cytometry and reverse transcription-quantitative polymerase chain reaction (PCR) were used to determine the polarization of macrophages. The conditioned medium of exosome-treated M0 cells was used to culture H1299 cells, and the Cell Counting Kit-8, Ki67, transwell and scratch wound assays were used to determine the biological behavior of H1299 cells. To investigate whether exosomal miR-146a regulates TAM macrophages through targeting tumor necrosis factor receptor-associated factor 6 (TRAF-6) and interleukin-1 receptor-associated kinase 1 (IRAK-1), we used small interfering RNA to knockdown the expressions of them. Results: Upregulation of miR-146a inhibited M1 polarization and thus impaired the antitumor activity of TAMs. Exosomes released by H1299 cells can be taken by M0 macrophage, and they upregulated the expression of miR-146a in M0 macrophage. The exosome suppresses M1 polarization by exosomal miR-146a. TRAF-6 and IRAK-1 mediated the inhibitive effects of exosomal miR-146a on M1 polarization. Conclusions: NSCLC cells released exosomal miR-146a to inhibit the expressions of TRAF-6 and IRAK-1 in TAMs, resulting in the impaired antitumor activity of TAMs. NSCLC cell-derived exosomal miR-146a represents a novel therapeutic target for NSCLC treatment.

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Идентификаторы

DOI: 10.21037/atm-22-5565

Цитирования и источники

Цитирований: 2Использованных источников: 0

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