基础医学与临床2024,Vol.44Issue(7):965-973,9.DOI:10.16352/j.issn.1001-6325.2024.07.0965
MAFB对肿瘤相关巨噬细胞极化及功能的影响
Impact of MAFB on polarization and function of tumor associated macrophages
摘要
Abstract
Objective To investigate the impact of the MAFB transcription factor on macrophage polarization phe-notype 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 hu-man acute monocytic leukaemia cell line(THP-1)was detected by RT-qPCR or Western blot.Detection of macro-phages 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 ability P>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.关键词
MAFB/巨噬细胞/M1/M2极化/吞噬作用/肿瘤杀伤效应Key words
MAFB/macrophage/M1/M2 polarization/phagocytosis/tumor cytotoxicity分类
基础医学引用本文复制引用
陈笑天,陈翀,罗云萍..MAFB对肿瘤相关巨噬细胞极化及功能的影响[J].基础医学与临床,2024,44(7):965-973,9.基金项目
国家自然科学基金(82273220,82373100) (82273220,82373100)
常州西太湖细胞前沿技术发展基金会重点培育项目(2022-P009) (2022-P009)