关键词: MAFB, 巨噬细胞, M1/M2极化, 吞噬作用, 肿瘤杀伤效应

Abstract: Objective To investigate the impact of the MAFB transcription factor on macrophage polarization phenotype and function. Methods Analysis of correlation of MAFB expression with survival period of patients of breast cancer and lung adenocarcinoma was performed by RNA-seq data from the Kaplan-Meier database. Flow cytometry was applied to detect MAFB expression in primary human monocytes. Expression of MAFB mRNA or protein of human acute monocytic leukaemia cell line(THP-1) was detected by RT-qPCR or Western blot. Detection of macrophages phenotypes was performed by macrophages polarization in vitro, co-culture, RT-qPCR and flow cytometry. Phagocytosis assay was used to assess changes in phagocytic ability of macrophages. In vitro killing assay to evaluate changes in tumor-killing ability of macrophages. Results Compared to the MAFB low-expression group, patients with high MAFB expression in breast cancer and lung adenocarcinoma exhibited a decreased survival period(P＜0.05). Protein interaction networks showed a correlation between MAFB protein and macrophage polarization proteins. Compared to other cell type, MAFB was specifically highly expressed in human monocyte-macrophage cells. Phorbol myristate ester(PMA) induced an increased MAFB expression in THP-1 cells (P＜0.05). Knockdown of MAFB inhibited the expression of M2-related genes (P＜0.05). Co-culture with tumor cells and knockdown of MAFB suppressed expression of polarization gene (P＜0.05). Knockdown of MAFB did not affect the phagocytic abilityP＞0.05) but enhanced tumor-killing ability of macrophages (P＜0.05). Conclusions This investigation proves potential function of MAFB transcription factor in regulation of macrophage M2 polarization and anti-tumor effect in solid tumors.

Key words: MAFB, macrophage, M1/M2 polarization, phagocytosis, tumor cytotoxicity