Suppressive role of SCN4B in the epithelial‑mesenchymal transition of lung adenocarcinoma.

The poor prognosis and high mortality rate of non‑small cell lung cancer are largely driven by its aggressive migratory and invasive behavior. Epithelial‑mesenchymal transition (EMT) is a central mechanism conferring these malignant traits. The present study examined the expression profile of the sodium channel β4 subunit (SCN4B) in lung adenocarcinoma (LUAD) and explored its regulatory role in EMT. Transcriptomic data from The Cancer Genome Atlas were analyzed to compare SCN4B expression between LUAD and normal tissues, and to assess its relationship with TNM clinical stage (I‑IV), overall survival and diagnostic performance using non‑parametric tests, Kaplan‑Meier analysis and receiver operating characteristic curves, respectively. Functional enrichment analysis, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and immune cell infiltration profiling were performed on SCN4B‑associated differentially expressed genes. In vitro, the A549 and H1299 LUAD cell lines were engineered to overexpress SCN4B. Viability, migration, invasion and apoptosis were evaluated using Cell Counting Kit‑8 assays, wound healing assays, Transwell assays and flow cytometry. In addition, western blotting was conducted to assess EMT markers, including E‑cadherin, N‑cadherin, Vimentin and Snail. The results demonstrated that SCN4B expression was markedly reduced in LUAD tissues and low SCN4B expression was associated with unfavorable clinical outcomes. KEGG analysis revealed enrichment of SCN4B‑related genes in the 'cell adhesion molecules' pathway, and SCN4B expression levels differed markedly between TNM tumor (T) pathologic stages T1 and T2. Furthermore, SCN4B overexpression suppressed viability, migration and invasion of A549 and H1299 cells, while promoting apoptosis. Western blotting demonstrated upregulation of E‑cadherin, and downregulation of N‑cadherin, Vimentin and Snail in the SCN4B overexpression group compared with the empty vector group, indicating inhibition of EMT. In conclusion, low SCN4B expression was associated with poor prognosis in LUAD. Notably, restoring SCN4B levels suppressed LUAD cell viability, migration and invasion in vitro, accompanied by inhibition of EMT. These findings highlighted SCN4B as a potential tumor suppressor and a promising therapeutic target for LUAD.