南方医科大学学报2025，Vol.45Issue(7)：1397-1408,12.DOI:10.12122/j.issn.1673-4254.2025.07.06
TGF-β通过miR-23a-3p/IRF1轴下调主要组织相容性复合体I类表达促进肝癌免疫逃逸
The TGF-β/miR-23a-3p/IRF1 axis mediates immune escape of hepatocellular carcinoma by inhibiting major histocompatibility complex class I
摘要
Abstract
Objective To investigate the mechanism by which transforming growth factor-β(TGF-β)regulates major histocompatibility complex class I(MHC-I)expression in hepatocellular carcinoma(HCC)cells and its role in immune evasion of HCC.Methods HCC cells treated with TGF-β alone or in combination with SB-431542(a TGF-β type I receptor inhibitor)were examined for changes in MHC-I expression using RT-qPCR and Western blotting.A RNA interference experiment was used to explore the role of miR-23a-3p/IRF1 signaling in TGF-β-mediated regulation of MHC-I.HCC cells with different treatments were co-cultured with human peripheral blood mononuclear cells(PBMCs),and the changes in HCC cell proliferation was assessed using CCK-8 and colony formation assays.T-cell cytotoxicity in the co-culture systems was assessed with lactate dehydrogenase(LDH)release and JC-1 mitochondrial membrane potential assays,and T-cell activation was evaluated by flow cytometric analysis of CD69 cells and ELISA for TNF-α secretion.Results TGF-β treatment significantly suppressed MHC-I expression in HCC cells and reduced T-cell activation,leading to increased tumor cell proliferation and decreased HCC cell death in the co-culture systems.Mechanistically,TGF-β upregulated miR-23a-3p,which directly targeted IRF1 to inhibit MHC-I transcription.Overexpression of miR-23a-3p phenocopied TGF-β-induced suppression of IRF1 and MHC-I.Conclusion We reveal a novel immune escape mechanism of HCC,in which TGF-β attenuates T cell-mediated antitumor immunity by suppressing MHC-I expression through the miR-23a-3p/IRF1 signaling axis.关键词
肝癌细胞/转化生长因子-β/主要组织相容性复合体I类/肿瘤免疫逃逸Key words
liver cancer cells/transforming growth factor-β/major histocompatibility complex class I/tumor immune escape引用本文复制引用
于滢,涂丽,刘洋,宋雪翼,邵倩倩,唐小龙..TGF-β通过miR-23a-3p/IRF1轴下调主要组织相容性复合体I类表达促进肝癌免疫逃逸[J].南方医科大学学报,2025,45(7):1397-1408,12.基金项目
国家自然科学基金(82071862) （82071862）
安徽理工大学医学专项培育项目(YZ2023H1A005)Supported by National Natural Science Foundation of China(82071862). （YZ2023H1A005）
