Blood Transfusion Department, Fuyang Normal University Affiliated Second Hospital, Fuyang, Anhui, 236000, China.
Fuyang Medical College, Fuyang Normal University, Fuyang, Anhui, 236037, China.
BMC Cancer. 2024 Feb 12;24(1):194. doi: 10.1186/s12885-024-11943-1.
Hepatocellular 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.
Downloading 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.
Bioinformatics 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.
TBRG4 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.
肝细胞癌（HCC）是最常见的恶性肝肿瘤，预后较差。本研究探讨了转化生长因子β调节剂 4（TBRG4）在 HCC 中的表达及其对 HCC 细胞增殖、侵袭和转移的影响，并分析了可能的分子机制。
下载 TCGA 数据库中 HCC 样本的表达和临床信息，通过生物信息学方法分析 TBRG4 的表达差异，分析临床相关性和预后意义。对患者 HCC 组织中 TBRG4 相关基因集进行 GO、KEGG 和 GSEA 富集分析。应用细胞计数、划痕试验和 Transwell 实验研究 TBRG4 在 HCC 中的生物学功能。评估线粒体膜电位、细胞凋亡和 ROS 水平以评估细胞铁死亡。应用 Western blot、RT-PCR、激光共聚焦显微镜和免疫共沉淀检测和分析 TBRG4 的下游信号通路和相互作用分子。
生物信息学分析显示，TBRG4 在 HCC 肿瘤组织中异常高表达，与 HCC 患者的不良预后和转移相关。GO 和 KEGG 功能富集分析显示，TBRG4 与氧化应激和 NADH 脱氢酶（泛醌）活性有关。GSEA 富集分析显示，TBRG4 与 Beta catenin 非依赖性 Wnt 信号和 B 细胞受体有关。功能实验证实，敲低 TBRG4 可抑制 HCC 细胞的增殖、迁移和侵袭。机制上，TBRG4 通过 DDX56/p-AKT/GSK3β 信号通路抑制 HCC 细胞的功能。此外，干扰 TBRG4 表达可降低 HCC 细胞的线粒体膜电位并积累 ROS，导致铁死亡增加。免疫共沉淀分析显示，TBRG4 特异性结合 Beclin1。
TBRG4 在 HCC 肿瘤组织中高表达，与预后不良相关。它可能通过 DDX56/p-AKT/GSK3β 信号通路调节 HCC 细胞的增殖、侵袭和转移。TBRG4 可能与 Beclin1 相互作用调节 HCC 细胞的铁死亡。
