Inhibition of inflammation and infiltration of M2 macrophages in NSCLC through the ATF3/CSF1 axis: Role of miR‐27a‐3p

Abstract

AbstractNon‐small cell lung cancer (NSCLC) imposes a significant economic burden on patients and society due to its low overall cure and survival rates. Tumour‐associated macrophages (TAM) affect tumour development and may be a novel therapeutic target for cancer. We collected NSCLC and tumour‐adjacent tissue samples. Compared with the tumour‐adjacent tissues, the Activation Transcription Factor 3 (ATF3) and Colony Stimulating Factor 1 (CSF‐1) were increased in NSCLC tissues. Levels of ATF3 and CSF‐1 were identified in different cell lines (HBE, A549, SPC‐A‐1, NCI‐H1299 and NCI‐H1795). Overexpression of ATF3 in A549 cells increased the expression of CD68, CD206 and CSF‐1. Moreover, levels of CD206, CD163, IL‐10 and TGF‐β increased when A549 cells were co‐cultured with M0 macrophages under the stimulation of CSF‐1. Using the starbase online software prediction and dual‐luciferase assays, we identified the targeting between miR‐27a‐3p and ATF3. Levels of ATF3, CSF‐1, CD206, CD163, IL‐10 and TGF‐β decreased in the miR‐27a mimics, and the tumour growth was slowed in the miR‐27a mimics compared with the mimics NC group. Overall, the study suggested that miR‐27a‐3p might inhibit the ATF3/CFS1 axis, regulate the M2 polarization of macrophages and ultimately hinder the progress of NSCLC. This research might provide a new therapeutic strategy for NSCLC.