Wang Tengkai, Zhang Hui, Feng Yaoyao, Yang Yinrong
Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China.
The First Clinical College of Shandong University, Jinan, Shandong, P.R. China.
Cancer Cell Int. 2025 Jul 28;25(1):288. doi: 10.1186/s12935-025-03926-4.
Gastric cancer (GC), an aggressive malignant tumor with poor overall survival worldwide, urgently requires novel diagnostic and therapeutic targets. The dyskeratosis congenita 1 (DKC1) gene has been reported to have diverse biological functions and prognostic values in several types of human cancers. However, the specific role and molecular mechanism of DKC1 in GC have received less attention.
Multi-omics analysis integrated The Cancer Genome Atlas (TCGA) data with validation in GC specimens and GC cell lines. DKC1 expression was quantified via immunohistochemistry, real-time polymerase chain reaction (qRT-PCR), and western blotting. Functional impacts on proliferation (CCK-8/cell cycle analysis), migration (Transwell), apoptosis (Annexin V/PI staining), and chemosensitivity (5-fluorouracil [5-FU] IC50) were assessed. RNA sequencing of DKC1-silenced AGS cells informed pathway enrichment (Gene Set Enrichment Analysis [GSEA]/Kyoto Encyclopedia of Genes and Genomes [KEGG]) to predict the underlying mechanism.
DKC1 expression was increased and displayed a remarkable diagnostic value in GC. High DKC1 expression correlated with advanced histologic grade and diffuse-type Lauren classification in GC patients. Functional studies revealed that DKC1 effectively promoted GC cell proliferation and migration while suppressing apoptosis in vitro. RNA-seq analysis and rescue experiments confirmed that DKC1 regulated GC progression via the NF-κB signaling pathway. Critically, DKC1 knockdown synergistically enhanced 5-FU efficacy through cell cycle dysregulation.
DKC1 was identified as a regulator of GC development through the NF-κB pathway. It displayed a dual role as a diagnostic biomarker and therapeutic target. Elevated DKC1 expression correlated with aggressive clinicopathological features and a good diagnostic value in GC. Furthermore, DKC1 knockdown synergistically enhanced 5-FU efficacy. These data suggested that DKC1 is a potential tumor diagnostic biomarker and a therapeutic target for GC.
胃癌（GC）是一种侵袭性恶性肿瘤，全球总体生存率较低，迫切需要新的诊断和治疗靶点。据报道，先天性角化不良1（DKC1）基因在几种人类癌症中具有多种生物学功能和预后价值。然而，DKC1在胃癌中的具体作用和分子机制尚未受到足够关注。
多组学分析整合了癌症基因组图谱（TCGA）数据，并在胃癌标本和胃癌细胞系中进行验证。通过免疫组织化学、实时聚合酶链反应（qRT-PCR）和蛋白质印迹法对DKC1表达进行定量。评估其对增殖（CCK-8/细胞周期分析）、迁移（Transwell）、凋亡（Annexin V/PI染色）和化疗敏感性（5-氟尿嘧啶[5-FU] IC50）的功能影响。对DKC1沉默的AGS细胞进行RNA测序，通过基因集富集分析（GSEA）/京都基因与基因组百科全书（KEGG）进行通路富集，以预测潜在机制。
DKC1表达增加，在胃癌中具有显著的诊断价值。DKC1高表达与胃癌患者的高级别组织学分级和弥漫型劳伦分类相关。功能研究表明，DKC1在体外可有效促进胃癌细胞增殖和迁移，同时抑制细胞凋亡。RNA测序分析和挽救实验证实，DKC1通过NF-κB信号通路调节胃癌进展。至关重要的是，DKC1敲低通过细胞周期失调协同增强了5-FU的疗效。
DKC1被确定为通过NF-κB途径调节胃癌发展的因子。它作为诊断生物标志物和治疗靶点具有双重作用。DKC1表达升高与侵袭性临床病理特征相关，在胃癌中具有良好的诊断价值。此外，DKC1敲低协同增强了5-FU的疗效。这些数据表明，DKC1是一种潜在的肿瘤诊断生物标志物和胃癌治疗靶点。
