Publication:
TRIM22 mechanism promoting KAT2A ubiquitination degradation to regulate ferroptosis in hepatocellular carcinoma cell invasion and metastasis

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Wang-40-1295-1307-2025.pdf(11.17 MB)
Date
2025
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Authors
Wang, Wei ; Chen, Xiaoshan ; Wei, Wei
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Publisher
Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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Biología Celular e Histología
DOI
https://doi.org/10.14670/HH-18-856
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info:eu-repo/semantics/article
Description
Abstract
Objective. Hepatocellular carcinoma (HCC) is a highly fatal cancer. This study aims to investigate the underlying mechanism of tripartite motif-containing 22 (TRIM22) in HCC cell invasion and metastasis through the K (lysine) acetyltransferase 2A (KAT2A)/ glutathione peroxidase 4 (GPX4) axis. Methods. Human HCC cells BEL7405 were cultured in vitro and treated with MG-132, Ferrostain-1, pcDNA3.1-TRIM22, pcDNA3.1-KAT2A, or pcDNA3.1-NC. TRIM22-KAT2A interaction and KAT2A ubiquitination level, cell proliferation, invasion, migration, and histone H3 lysine 9 acetylation (H3K9ac) enrichment level on the GPX4 promoter were assessed by Co-IP, CCK-8, Transwell, and ChIP-qPCR assays. Mice were injected subcutaneously with Lv-oe-NC or Lv-oe-TRIM22 BEL7405 cells via the tail vein. Tumor proliferation and levels of TRIM22, KAT2A, GPX4, Fe2+, malondialdehyde (MDA), reactive oxygen species (ROS), and glutathione (GSH) in tissues and cells were evaluated by immunohistochemistry, RT-qPCR, western blot, and kits. Results. oe-TRIM22-treated BEL7405 cells exhibited increased TRIM22 expression, and abated KAT2A protein expression and malignant cell biological behaviors, which were partially reversed by upregulating KAT2A or suppressing ferroptosis. TRIM22 interacted with KAT2A, which was ubiquitinated to regulate GPX4 histone acetylation. TRIM22 overexpression elevated Fe2+, MDA, and ROS levels and cell death, and diminished GSH, GPX4, and H3K9ac enrichment levels, whereas further overexpression of KAT2A brought about opposite trends. TRIM22 suppressed HCC growth and metastasis by mediating ferroptosis through the KAT2A/GPX4 axis. Conclusions. TRIM22 promoted KAT2A ubiquitina-tion degradation to reduce H3K9ac enrichment levels in the GPX4 promoter region, and facilitated ferroptosis, thereby inhibiting HCC cell invasion and metastasis and in vivo growth and metastasis.
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Ubiquitination degradation , Ferroptosis , Tripartite motif-containing 22 (TRIM22) , K (lysine) acetyltransferase 2A (KAT2A) , Glutathione peroxidase 4 (GPX4) , Invasion , Metastasis
Citation
Histology and Histopathology Vol. 40, nº08 (2025)
URI
http://hdl.handle.net/10201/157356
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Histology and histopathology Vol.40, nº8 (2025)
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