You Qi, Huang Tao, He Zhijie, Tao Xinlu, Zhang Yan, Zhang Haotian, Zhu Shaojin
Department of Thoracic Surgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, China.
Transl Cancer Res. 2025 May 30;14(5):2648-2660. doi: 10.21037/tcr-24-2075. Epub 2025 Apr 27.
Lung adenocarcinoma (LUAD) is a prevalent malignancy characterized by low survival rates and poor prognosis. Gap junction beta-2 protein () is overexpressed in various tumors and is associated with cancer stem cell (CSC) properties. However, its role in LUAD remains unclear. This study explored the regulatory mechanism of in promoting CSC properties of LUAD.
Differentially expressed genes (DEGs) related to CSC properties were analyzed using the Gene Expression Omnibus (GEO) and Gene Expression Profiling Interactive Analysis 2 (GEPIA 2) databases. Protein expression was assessed via western blotting, and gene expression was quantitative real-time polymerase chain reaction (qRT-PCR) in LUAD cell lines. Loss-of-function experiments were performed to evaluate the impact of on cell proliferation, apoptosis, and migration. CSC properties were confirmed through sphere formation assay and flow cytometry of CD133+/CD44+cells. Promoter activity was examined using a dual-luciferase reporter assay.
GJB2 was associated with the CSC properties in LUAD, with its expression upregulated in LUAD cell lines. GJB2 downregulation impaired proliferation, reduced migration, and induced apoptosis in A549 and H1299 cells. Mechanistically, activated the nuclear factor kappa-B (NF-κB) pathway, facilitating the nuclear translocation of p65 and enhancing sex-determining region Y-Box 2 () transcription.
promotes transcription and enhances CSC properties in LUAD by modulating NF-κB pathway activity.
肺腺癌（LUAD）是一种常见的恶性肿瘤，其生存率低且预后不良。缝隙连接β-2蛋白（GJB2）在多种肿瘤中过度表达，并与癌症干细胞（CSC）特性相关。然而，其在LUAD中的作用仍不清楚。本研究探讨了GJB2促进LUAD的CSC特性的调控机制。
使用基因表达综合数据库（GEO）和基因表达谱交互式分析2（GEPIA 2）数据库分析与CSC特性相关的差异表达基因（DEG）。通过蛋白质印迹法评估蛋白质表达，并在LUAD细胞系中采用定量实时聚合酶链反应（qRT-PCR）检测基因表达。进行功能丧失实验以评估GJB2对细胞增殖、凋亡和迁移的影响。通过成球实验和CD133+/CD44+细胞的流式细胞术确认CSC特性。使用双荧光素酶报告基因检测法检测启动子活性。
GJB2与LUAD中的CSC特性相关，其在LUAD细胞系中的表达上调。GJB2下调会损害A549和H1299细胞的增殖、减少迁移并诱导凋亡。机制上，GJB2激活核因子κB（NF-κB）途径，促进p65的核转位并增强性别决定区Y框蛋白2（SOX2）转录。
GJB2通过调节NF-κB途径活性促进SOX2转录并增强LUAD中的CSC特性。
