The TGF-β/miR-23a-3p/IRF1 axis mediates immune escape of hepatocellular carcinoma by inhibiting major histocompatibility complex class I
YU Ying
TU Li
LIU Yang
SONG Xueyi
SHAO Qianqian
TANG Xiaolong
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.
Keywords：liver cancer cellstransforming growth factor-βmajor histocompatibility complex class Itumor immune escape
Publication Date：2025-07-20
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：12( 1397-1408 )