Chen Zhuo, Ding Yu-Heng, Zhao Mei-Qi, Zhang Yong-Jun, Sun Meng-Ying, Zhang Ai-Qin, Qian Xiang, Ji Xu-Ming
School of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Department of Traditional Chinese Medicine, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
Front Oncol. 2025 Mar 25;15:1543463. doi: 10.3389/fonc.2025.1543463. eCollection 2025.
Lung adenocarcinoma (LUAD) is the primary subtype of Non-small cell lung cancer (NSCLC) and a serious threat to human health. However, the precise molecular mechanisms in lung cancer remain largely unexplored.
Herein, we performed proteomic analysis in a cohort of 20 LC primary tumors and their paired normal tissues. The expression levels and prognostic value of hub proteins were also explored in LUAD using public databases. Glycinamide ribonucleotide transformylase (GART) expression was detected by qRT-PCR in LC cell lines. The roles of GART were assessed by CCK-8, colony formation, Wound healing assays, and xenograft tumor model. Expression levels of the PAICS-Akt-β-catenin pathway were estimated through qRT-PCR and western blot assays.
The proteomic analysis of tumor tissues of LC indicated that 263 proteins were upregulated and 194 were downregulated. Bioinformatics analysis showed that differentially expressed proteins were mainly associated with the regulation of apoptotic process and cell adhesion, PI3K-Akt signaling pathway, Purine metabolism, and Wnt signaling pathway. The expression of hub proteins EPRS, GART, HSPE1, and RPS6 was much higher in LUAD tissues than in normal tissues analyzed by the Ualcan database. Overexpression of GART represented a poor prognosis in LUAD patients. Additionally, the knockdown of GART effectively inhibited the cell proliferation and migration of LC cells both and Mechanistically, qRT-PCR and western blot analyses suggested that GART deletion could inhibit the activation of the PAICS-Akt-β-catenin pathway .
Our study indicated a tumor-promoting function of GART in LC through the regulation of the PAICS-Akt-β-catenin axis, and it may be used as a therapeutic target for NSCLC.
肺腺癌（LUAD）是非小细胞肺癌（NSCLC）的主要亚型，对人类健康构成严重威胁。然而，肺癌的确切分子机制在很大程度上仍未被探索。
在此，我们对20例肺癌原发肿瘤及其配对的正常组织进行了蛋白质组学分析。还使用公共数据库在肺腺癌中探索了枢纽蛋白的表达水平和预后价值。通过qRT-PCR检测肺癌细胞系中甘氨酰胺核糖核苷酸转甲酰基酶（GART）的表达。通过CCK-8、集落形成、伤口愈合试验和异种移植肿瘤模型评估GART的作用。通过qRT-PCR和蛋白质免疫印迹分析评估PAICS-Akt-β-连环蛋白信号通路的表达水平。
肺癌肿瘤组织的蛋白质组学分析表明，263种蛋白质上调，194种蛋白质下调。生物信息学分析表明，差异表达的蛋白质主要与凋亡过程调控、细胞黏附、PI3K-Akt信号通路、嘌呤代谢和Wnt信号通路相关。通过Ualcan数据库分析，枢纽蛋白EPRS、GART、HSPE1和RPS6在肺腺癌组织中的表达远高于正常组织。GART的过表达代表肺腺癌患者预后不良。此外，敲低GART可有效抑制肺癌细胞的增殖和迁移。机制上，qRT-PCR和蛋白质免疫印迹分析表明，GART缺失可抑制PAICS-Akt-β-连环蛋白信号通路的激活。
我们的研究表明，GART通过调节PAICS-Akt-β-连环蛋白轴在肺癌中发挥促肿瘤作用，它可能作为非小细胞肺癌的治疗靶点。
