biostudies-literatureUnknown10(24)Yan Z<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.Annals of translational medicine1307https://www.ebi.ac.uk/biostudies/studies/S-EPMC9843328biostudies-literatureTumor cell-derived exosomal microRNA-146a promotes non-small cell lung cancer cell invasion and proliferation by inhibiting M1 macrophage polarization.PMC9843328Yan LZheng WQWen XHZhao WZhang MWang YFWang YJHu ZDYan ZCao XSHan YLHai LWen JXfalseTumor cell-derived exosomal microRNA-146a promotes non-small cell lung cancer cell invasion and proliferation by inhibiting M1 macrophage polarization.<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.2022-01-01T00:00:00Z2022 Dec2025-04-04T08:29:25.642Z2025-04-04T08:29:25.642ZS-EPMC98433283666062310.21037/atm-22-5565