CLIC4 inhibits the progression of non-small cell lung cancer by suppressing the MAPK pathway

In addition to its involvement in maintaining membrane electrical balance, ion homeostasis, and transmembrane transport, intracellular chloride channel protein 4 (CLIC4) is regulated by signaling molecules such as TGF-β, P53, Myc, and TNFα and is closely associated with apoptosis. Nevertheless, the expression patterns and functional roles of CLIC4 across different cancer types remain inconsistent and are not fully understood. In this study, we initially observed reduced CLIC4 expression in non-small cell lung cancer (NSCLC) through bioinformatics analysis and further validated this downregulation using multidimensional experimental approaches. We established stable NSCLC cell lines with CLIC4 overexpression or knockdown to investigate its effects on cellular proliferation, migration, and invasion. Subsequent RNA sequencing of CLIC4-overexpressing cells revealed that CLIC4 suppressed MAPK-related signaling pathways, which was confirmed by western blotting. These findings suggest that CLIC4 may inhibit the progression of NSCLC by downregulating MAPK signaling, offering potential insights for novel diagnostic and therapeutic strategies in NSCLC.