Chen Zhimeng, Shi Hao, Hu Wenxuan, Yang Jian, Xing Yuxuan, Lv Xin, Wu Chenzhuo, Ding Cheng, Zhao Jun
Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, 899 Ping Hai Road, Suzhou, 215000, Jiangsu, China.
Institute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
Sci Rep. 2025 May 13;15(1):16590. doi: 10.1038/s41598-025-01611-0.
LUAD, a prevalent lung cancer with high mortality, has seen increased focus on molecular targeted therapies due to patient heterogeneity. Among these prospects, dystrophin-associated protein 2 (DRP2), a critical component of the dystrophin complex, underpins membrane-associated structures vital for intercellular interactions in vertebrates. Aberrations in DRP2 function have been linked to the occurrence and development of multiple diseases, prompting an inquiry into its potential link with LUAD progression. To delve into the potential roles of DRP2 in LUAD, we initiated a comprehensive investigation. First, we analyzed DRP2 expression patterns in LUAD using bioinformatics tools. This was subsequently validated through immunohistochemical staining, quantitative PCR, and Western blot analyses. Furthermore, we assessed the functional implications of DRP2 in LUAD cells, both in vitro and in vivo, utilizing assays such as cell cycle analysis, CCK-8 proliferation assay, Colony formation assay EdU incorporation, Transwell migration test, scratch wound healing assay, flow cytometry, and mouse models for tumor xenograft and metastasis. Results showed a strong correlation between high DRP2 expression in LUAD and poorer survival. Notably, DRP2 knockdown accelerated LUAD progression via the EMT pathway. These findings highlight DRP2's crucial role in LUAD and its potential as a therapeutic target.
肺腺癌(LUAD)是一种常见且死亡率高的肺癌,由于患者的异质性,分子靶向治疗受到了更多关注。在这些研究前景中,肌营养不良蛋白相关蛋白2(DRP2)是肌营养不良蛋白复合体的关键组成部分,它支撑着对脊椎动物细胞间相互作用至关重要的膜相关结构。DRP2功能异常与多种疾病的发生和发展有关,这促使人们探究其与LUAD进展之间的潜在联系。为了深入研究DRP2在LUAD中的潜在作用,我们展开了全面调查。首先,我们使用生物信息学工具分析了LUAD中DRP2的表达模式。随后通过免疫组织化学染色、定量PCR和蛋白质印迹分析对其进行了验证。此外,我们利用细胞周期分析、CCK-8增殖试验、集落形成试验、EdU掺入、Transwell迁移试验、划痕伤口愈合试验、流式细胞术以及肿瘤异种移植和转移的小鼠模型等实验,在体外和体内评估了DRP2在LUAD细胞中的功能影响。结果显示,LUAD中DRP2高表达与较差的生存率密切相关。值得注意的是,敲低DRP2会通过上皮-间质转化(EMT)途径加速LUAD的进展。这些发现突出了DRP2在LUAD中的关键作用及其作为治疗靶点的潜力。