The TGF‑β/miR-23a-3p/IRF1 axis mediates immune escape of hepatocellular carcinoma by inhibiting major histocompatibility complex class I.
10.12122/j.issn.1673-4254.2025.07.06
- Author:
Ying YU
1
;
Li TU
1
;
Yang LIU
1
;
Xueyi SONG
1
;
Qianqian SHAO
1
;
Xiaolong TANG
1
Author Information
1. School of Medicine, Anhui University of Science and Technology, Huainan 232001, China.
- Publication Type:Journal Article
- Keywords:
liver cancer cells;
major histocompatibility complex class I;
transforming growth factor-β;
tumor immune escape
- MeSH:
Humans;
MicroRNAs/genetics*;
Carcinoma, Hepatocellular/metabolism*;
Liver Neoplasms/metabolism*;
Interferon Regulatory Factor-1/metabolism*;
Transforming Growth Factor beta/metabolism*;
Signal Transduction;
Histocompatibility Antigens Class I/metabolism*;
Cell Line, Tumor;
Tumor Escape;
Coculture Techniques
- From:
Journal of Southern Medical University
2025;45(7):1397-1408
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES: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.
CONCLUSIONS: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.
