Yang Xingyu, Ma Bingfeng, Liu Yafeng, Zhou Jiawei, Guo Jianqiang, Peng Yuanyuan, Bai Ying, Wu Jing, Hu Dong
Department of Immunology, School of Medicine, Anhui University of Science and Technology, Huainan City, China; Anhui Province Engineering Laboratory of Occupational Health and Safety, School of Medicine, Anhui University of Science and Technology, Huainan City, China.
Department of Immunology, School of Medicine, Anhui University of Science and Technology, Huainan City, China; Anhui Province Engineering Laboratory of Occupational Health and Safety, School of Medicine, Anhui University of Science and Technology, Huainan City, China; Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, School of Medicine, Anhui University of Science and Technology, Huainan City, China.
Cell Signal. 2025 Mar;127:111552. doi: 10.1016/j.cellsig.2024.111552. Epub 2024 Dec 4.
Progression of lung adenocarcinoma (LUAD) is frequently associated with alterations in epithelial-mesenchymal transition (EMT) and cell cycle. Our study analyzed the Cancer Genome Atlas (TCGA) database and identified a positive correlation between high expression of SSBP1 in LUAD tumor tissues and poor prognosis (p < 0.05), with an AUC of 0.853, suggesting that SSBP1 could serve as a prognostic biomarker. In vitro experiments, including siRNA-mediated SSBP1 knockdown and subsequent cell cloning and Transwell assays, revealed significant inhibition of proliferation, migration, and cell cycle progression in LUAD cells (p < 0.05). In vivo mouse model experiments further confirmed that SSBP1 knockdown inhibits tumor burden (p < 0.05). Mechanistic investigations, integrating pathway enrichment analysis with molecular biology techniques, identified RRM2 as a downstream target of SSBP1, and RRM2 knockdown similarly suppressed LUAD cell proliferation, migration, and cell cycle progression (p < 0.05). These findings indicate that SSBP1 promotes EMT and cell cycle progression in LUAD cells by positively regulating RRM2, thereby accelerating disease progression. Collectively, our study not only confirms the potential role of SSBP1 in LUAD but also provides a theoretical foundation for therapeutic strategies targeting the SSBP1/RRM2 axis, potentially offering new therapeutic targets for LUAD patients.
肺腺癌(LUAD)的进展通常与上皮-间质转化(EMT)和细胞周期的改变有关。我们的研究分析了癌症基因组图谱(TCGA)数据库,发现LUAD肿瘤组织中SSBP1高表达与预后不良呈正相关(p < 0.05),曲线下面积(AUC)为0.853,这表明SSBP1可作为一种预后生物标志物。体外实验,包括小干扰RNA(siRNA)介导的SSBP1敲低以及随后的细胞克隆和Transwell实验,显示LUAD细胞的增殖、迁移和细胞周期进程受到显著抑制(p < 0.05)。体内小鼠模型实验进一步证实,SSBP1敲低可抑制肿瘤负荷(p < 0.05)。通过将通路富集分析与分子生物学技术相结合的机制研究,确定RRM2为SSBP1的下游靶点,敲低RRM2同样可抑制LUAD细胞的增殖、迁移和细胞周期进程(p < 0.05)。这些发现表明,SSBP1通过正向调节RRM2促进LUAD细胞的EMT和细胞周期进程,从而加速疾病进展。总体而言,我们的研究不仅证实了SSBP1在LUAD中的潜在作用,还为针对SSBP1/RRM2轴的治疗策略提供了理论基础,可能为LUAD患者提供新的治疗靶点。