Department of Thoracic Surgery, The First Hospital of Putian, The School of Clinical Medicine, Fujian Medical University Putian, Fujian, 351100, China.
Sci Rep. 2024 Apr 15;14(1):8694. doi: 10.1038/s41598-024-58539-0.
We aimed to investigate the expression and clinic significance of Rac GTPase Activating Protein 1 (RACGAP1) in human lung adenocarcinoma (LUAD). Online database analysis revealed a significant increase in RACGAP1 mRNA expression among 26 types of tumor tissues, including LUAD tissues. Online database and tissue microarray analyses indicated that RACGAP1 expression was significantly upregulated in LUAD tissues. Genetic variation analysis identified four different genetic variations of RACGAPs in LUAD. Moreover, online database analysis showed that RACGAP1 upregulation was correlated with shorter survival in patients with LUAD. After silencing RACGAP1 expression in A549 cells using siRNA and assessing its protein levels via Western blotting, we found that RACGAP1 knockdown inhibited cell growth and induced apoptosis determined using the Cell Counting Kit-8 assay, colony formation assay, and flow cytometry. Mechanistically, western blot analysis indicated that Bax expression increased, whereas Bcl-2 expression decreased. Moreover, RACGAP1 knockdown attenuated PI3K/AKT pathway activation in lung cancer cells. Taken together, our findings showed that RACGAP1 was overexpressed in LUAD tissues and played an important role in lung cancer by increasing cell growth through the PI3K/AKT signaling pathway. This study suggests recommends evaluating RACGAP1 in clinical settings as a novel biomarker and potential therapeutic target for lung cancer.
我们旨在研究 Rac GTPase 激活蛋白 1(RACGAP1)在人肺腺癌(LUAD)中的表达及其临床意义。在线数据库分析显示,在包括 LUAD 组织在内的 26 种肿瘤组织中,RACGAP1 mRNA 表达显著增加。在线数据库和组织微阵列分析表明,RACGAP1 在 LUAD 组织中表达显著上调。遗传变异分析鉴定出 LUAD 中存在四种不同的 RACGAP 遗传变异。此外,在线数据库分析显示,RACGAP1 的上调与 LUAD 患者的生存时间缩短相关。通过使用 siRNA 沉默 A549 细胞中的 RACGAP1 表达并通过 Western blot 评估其蛋白水平,我们发现 RACGAP1 敲低抑制了细胞生长并通过细胞计数试剂盒-8 测定、集落形成测定和流式细胞术诱导细胞凋亡。机制上,Western blot 分析表明 Bax 表达增加,而 Bcl-2 表达减少。此外,RACGAP1 敲低减弱了肺癌细胞中 PI3K/AKT 通路的激活。总之,我们的研究结果表明,RACGAP1 在 LUAD 组织中过表达,并通过 PI3K/AKT 信号通路增加细胞生长,在肺癌中发挥重要作用。本研究建议在临床环境中评估 RACGAP1 作为一种新的生物标志物和潜在的肺癌治疗靶点。