Cai Yuyin, Lu Xinyan, Li Tingting, Liu Jia, Jiang Lifeng
Thoracic Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650101, China.
Oncology Department, The Second Affiliated Hospital of Kunming Medical University, No. 374 Dianmian Avenue, Wuhua District, Kunming, Yunnan, 650101, China.
J Cardiothorac Surg. 2025 May 28;20(1):244. doi: 10.1186/s13019-025-03481-z.
Among malignant tumors, non-small cell lung cancer (NSCLC) remains a major threat to human life and health. Studies have illustrated that minichromosome maintenance protein 4 (MCM4) has complex interactions with the progression of many cancers, yet the role and mechanism of MCM4 in NSCLC remain to be elucidated.
MCM4 expression in NSCLC tissues was assessed using the TCGA database. MCM4 levels in NSCLC cells and tissues was validated utilizing qRT-PCR and western blot. Cell proliferation, metastasis and EMT were measured by CCK-8, transwell, and western blot assays. Subsequently, E2F1 bound with the promoter of MCM4 was predicted via JASPAR database. Luciferase assay and chromatin immunoprecipitation (ChIP) were utilized to evaluate the binding relationship between the two. Finally, rescue experiments were performed to demonstrate the mechanism of MCM4 regulating NSCLC progression. Xenograft model was utilized to prove the role of MCM4 and E2F1 in NSCLC in vivo.
MCM4 was markedly elevated in NSCLC tumor samples and intimately linked to poor patient prognosis. Silencing of MCM4 repressed growth, migration, invasion, and EMT of cells. In vivo test findings displayed that knockdown of MCM4 suppressed changes in tumor volume and weight in mice. Moreover, E2F1 bound with the promoter of MCM4 was predicted by JASPAR database. E2F1 was heightened in NSCLC tissues and cells. Then, the outcome of rescue assays confirmed that E2F1 introduction attenuated the depressing influence of MCM4 knockdown on NSCLC. Moreover, E2F1/MCM4 promoted the progression of NSCLC by activating the PI3K/AKT signaling pathway.
E2F1 accelerated NSCLC progression by activating the PI3K/AKT pathway through MCM4. Our outcomes confirmed that MCM4 is a potential target for the treatment of NSCLC patients.
在恶性肿瘤中，非小细胞肺癌（NSCLC）仍然是对人类生命和健康的主要威胁。研究表明，微小染色体维持蛋白4（MCM4）与多种癌症的进展存在复杂的相互作用，但MCM4在NSCLC中的作用和机制仍有待阐明。
使用TCGA数据库评估NSCLC组织中MCM4的表达。利用qRT-PCR和蛋白质印迹法验证NSCLC细胞和组织中MCM4的水平。通过CCK-8、Transwell和蛋白质印迹分析检测细胞增殖、转移和上皮-间质转化（EMT）。随后，通过JASPAR数据库预测与MCM4启动子结合的E2F1。利用荧光素酶报告基因检测和染色质免疫沉淀（ChIP）评估两者之间的结合关系。最后，进行挽救实验以证明MCM4调节NSCLC进展的机制。利用异种移植模型在体内证明MCM4和E2F1在NSCLC中的作用。
MCM4在NSCLC肿瘤样本中显著升高，且与患者预后不良密切相关。MCM4沉默可抑制细胞的生长、迁移、侵袭和EMT。体内试验结果显示，敲低MCM4可抑制小鼠肿瘤体积和重量的变化。此外，JASPAR数据库预测E2F1与MCM4启动子结合。E2F1在NSCLC组织和细胞中升高。然后，挽救实验结果证实，引入E2F1可减弱MCM4敲低对NSCLC的抑制作用。此外，E2F1/MCM4通过激活PI3K/AKT信号通路促进NSCLC的进展。
E2F1通过MCM4激活PI3K/AKT途径加速NSCLC进展。我们的结果证实MCM4是治疗NSCLC患者的潜在靶点。
