Highly expressed GCN1 is associated with cancer progression and poor prognosis in hepatocellular carcinoma patients.

IF 6 2区 医学 Q1 ONCOLOGY Cancer Cell International Pub Date : 2025-03-20 DOI:10.1186/s12935-025-03732-y
Zhongchao Zhang, Caijun Rao, Mingcun Hu, Wei Yan, Zhipeng Du
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Abstract

Background: General control non-derepressible protein 1 (GCN1), a ribosome-binding protein, has been implicated in the development and progression of multiple cancers. However, the potential role of GCN1 in hepatocellular carcinoma (HCC) has not yet been investigated.

Methods: The expression of GCN1 in HCC was analyzed using multiple databases. Bioinformatics analysis was employed to investigate the correlation of GCN1 expression with clinical significance and immune infiltration in HCC. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, gene set enrichment analysis (GSEA), and in vitro experiments were conducted to study the function and potential mechanisms of GCN1 in HCC.

Results: GCN1 was significantly upregulated in HCC, which was associated with worse clinicopathological features and poorer prognosis of the patients. GCN1 expression was closely associated with immune cell infiltration in HCC. GSEA analysis showed that GCN1 was involved in several tumor-related signaling pathways, including cell cycle, DNA replication, and Wnt signaling pathway. Knockdown of GCN1 inhibited the proliferation, invasion and migration of HCC cells, and also down-regulated the expression levels of cell cycle protein cyclin B1 (CCNB1), cyclin D1 (CCND1), and Wnt signaling pathway-related proteins Wnt3A and β-catenin.

Conclusion: GCN1 overexpression was associated with HCC progression and poor prognosis, and GCN1 knockdown could suppress the proliferation, migration and invasion ability of HCC cells by regulating Wnt signaling pathway, suggesting the potential of GCN1 as a prognostic and therapeutic target for HCC.

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高表达的 GCN1 与肝细胞癌患者的癌症进展和预后不良有关。
背景:一般控制非抑制蛋白1 (GCN1)是一种核糖体结合蛋白,参与多种癌症的发生和进展。然而,GCN1在肝细胞癌(HCC)中的潜在作用尚未被研究。方法:采用多数据库分析GCN1在HCC中的表达。采用生物信息学分析探讨GCN1表达与HCC临床意义及免疫浸润的相关性。通过京都基因与基因组百科全书(KEGG)富集分析、基因集富集分析(GSEA)和体外实验研究GCN1在HCC中的功能和潜在机制。结果:GCN1在HCC中显著上调,与患者临床病理特征恶化、预后较差相关。GCN1表达与肝细胞癌免疫细胞浸润密切相关。GSEA分析显示GCN1参与多种肿瘤相关信号通路,包括细胞周期、DNA复制和Wnt信号通路。GCN1的下调抑制了HCC细胞的增殖、侵袭和迁移,下调了细胞周期蛋白cyclin B1 (CCNB1)、cyclin D1 (CCND1)、Wnt信号通路相关蛋白Wnt3A和β-catenin的表达水平。结论:GCN1过表达与HCC的进展及预后不良相关,GCN1敲低可通过调节Wnt信号通路抑制HCC细胞的增殖、迁移和侵袭能力,提示GCN1有作为HCC预后和治疗靶点的潜力。
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来源期刊
CiteScore
10.90
自引率
1.70%
发文量
360
审稿时长
1 months
期刊介绍: Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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