Journal Article

Transcription factor E2F1 promotes non-small cell lung cancer progression by activating the PI3K/AKT pathway through MCM4

Li, Tingting, Jiang, Lifeng, Lu, Xinyan, Liu, Jia, Cai, Yuyin

2025

Overview

Purpose 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. Methods 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. Results 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. Conclusions 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: 1-Phosphatidylinositol 3-kinase / AKT protein / Animals / Antibodies / Assaying / Biomarkers / Cancer / Carcinoma, Non-Small-Cell Lung - genetics / Carcinoma, Non-Small-Cell Lung - metabolism / Carcinoma, Non-Small-Cell Lung - pathology / Cardiac Surgery / Cell cycle / Cell Line, Tumor / Cell Proliferation / Cholecystokinin / Chromatin / Development and progression / Disease Progression / E2F1 / E2F1 Transcription Factor - genetics / E2F1 Transcription Factor - metabolism / Enzymes / Female / Gene Expression Regulation, Neoplastic / Glioma / Humans / Immunoprecipitation / In vivo methods and tests / Liver cancer / Lung cancer / Lung cancer, Non-small cell / Lung cancer, Small cell / Lung Neoplasms - genetics / Lung Neoplasms - metabolism / Lung Neoplasms - pathology / Male / MCM4 / Medical prognosis / Medicine / Medicine & Public Health / Metastases / Mice / Mice, Nude / Minichromosome Maintenance Complex Component 4 - genetics / Minichromosome Maintenance Complex Component 4 - metabolism / Non-small cell lung carcinoma / NSCLC / Oncology, Experimental / Patients / Phosphatidylinositol 3-Kinases - genetics / Phosphatidylinositol 3-Kinases - metabolism / Plasmids / Progression / Proteins / Proto-Oncogene Proteins c-akt - genetics / Proto-Oncogene Proteins c-akt - metabolism / Reagents / Signal Transduction / Small cell lung carcinoma / Thoracic Surgery / Tumors / Variance analysis / Xenograft model / Xenotransplantation