ArticleBMC cancer2024
High expression of TBRG4 in relation to unfavorable outcome and cell ferroptosis in hepatocellular carcinoma.
Article in BMC cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 9 citations in OpenAlex.
- DDX59-AS1: A Novel Prognostic Biomarker and Immunotherapy Predictor in Lung Adenocarcinoma.Current medicinal chemistry · 2026Article
- TSPOAP1-AS1: A Novel Biomarker for the Prognosis and Therapeutic Target in Cervical Cancer.Combinatorial chemistry & high throughput screening · 2026Article
- The Role of Mitochondrial Complexes in Liver Diseases.Journal of clinical and translational hepatology · 2025Review
- Knockdown of TBRG4 suppresses the migration, invasion, and epithelial-to-mesenchymal transition of pancreatic cancer cells via TGF-β/smad3 signaling.Histology and histopathology · 2025Article
- Insights into the E2F target genes in breast cancer: associations of pathway genes with prognosis and immune cell filtration based on in silico and ex vivo analyses.Cancer cell international · 2025Article
- Comprehensive analysis of regulatory B Cell related genes in prognosis and therapeutic response in lung adenocarcinoma.Frontiers in immunology · 2025Article
- LNX1-AS2 as a Key Prognostic and Immunotherapy Response Biomarker for Lung Adenocarcinoma.Current medicinal chemistry · 2025Article
- NOP56 interacts with Fibrarin to regulate the PI3K/AKT signaling pathway and inhibit apoptosis of hepatocellular carcinoma.Frontiers in oncology · 2025Article
- Targeting cell death mechanisms: the potential of autophagy and ferroptosis in hepatocellular carcinoma therapy.Frontiers in immunology · 2024Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundHepatocellular carcinoma (HCC) is the most common type of malignant liver tumor with poor prognosis. In this study, we investigated the expression of transforming growth factor beta regulator 4 (TBRG4) in HCC and its effects on the proliferation, invasion, and metastasis of HCC cells, and analyzed the possible molecular mechanisms.
methodDownloading the expression and clinical information of HCC samples in the TCGA database, analyzing the expression differences of TBRG4 by bioinformatics methods, analyzing the clinical relevance and prognostic significance. Performing GO, KEGG and GSEA enrichment analysis on the TBRG4-related gene set in patient HCC tissues. Applying cell counting, scratch test and Transwell experiment to study the biological function of TBRG4 in HCC. Mitochondrial membrane potential, apoptosis and ROS levels were evaluated to assess cell iron death. Western blot, RT-PCR, laser confocal microscopy and co-immunoprecipitation were used to detect and analyze the downstream signaling pathways and interacting molecules of TBRG4.
resultsBioinformatics analysis revealed that TBRG4 was abnormally highly expressed in HCC tumor tissues and was associated with poor prognosis and metastasis in HCC patients. GO and KEGG functional enrichment analysis showed that TBRG4 was related to oxidative stress and NADH dehydrogenase (ubiquinone) activity. GSEA enrichment analysis showed that TBRG4 was associated with Beta catenin independent wnt signaling and B cell receptor. Functional experiments confirmed that knocking down TBRG4 could inhibit the proliferation, migration, and invasion of HCC cells. Mechanistically, TBRG4 inhibited the function of HCC cells through the DDX56/p-AKT/GSK3β signaling pathway. In addition, interference with TBRG4 expression could reduce the mitochondrial membrane potential and accumulate ROS in HCC cells, leading to increased ferroptosis. Co-IP analysis showed that TBRG4 specifically bound to Beclin1.
conclusionTBRG4 is highly expressed in HCC tumor tissues and is associated with poor prognosis. It may regulate the proliferation, invasion, and metastasis of HCC cells through the DDX56/p-AKT/GSK3β signaling pathway. TBRG4 may interact with Beclin1 to regulate the ferroptosis of HCC cells.
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