GJB2 enhances cancer stem cell properties by modulating SOX2 expression via NF-κB pathway activation in lung adenocarcinoma.

Abstract

Background: Lung adenocarcinoma (LUAD) is a prevalent malignancy characterized by low survival rates and poor prognosis. Gap junction beta-2 protein (GJB2) 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 GJB2 in promoting CSC properties of LUAD.

Methods: 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 GJB2 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.

Results: 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, GJB2 activated the nuclear factor kappa-B (NF-κB) pathway, facilitating the nuclear translocation of p65 and enhancing sex-determining region Y-Box 2 (SOX2) transcription.

Conclusions: GJB2 promotes SOX2 transcription and enhances CSC properties in LUAD by modulating NF-κB pathway activity.