IL-17E facilitates cell proliferation and epithelial-mesenchymal transition in A549 NSCLC cells by regulating the NF-κB pathway

Abstract

Objective

Interleukin-17 E (IL-17E) is a pro-inflammatory cytokine that participates in the inflammatory response and tumorigenesis. However, the function of IL-17E in non-small cell lung cancer (NSCLC) remains largely unknown.

Methods

The clinical value of IL-17E was determined by immunohistochemistry (IHC) in 75 cases of NSCLC tissues. Furthermore, A549 cells were added with recombinant human IL-17E (rhIL-17E) or transfected with IL-17E siRNAs to evaluate the impact on cell proliferation, apoptosis, and epithelial-mesenchymal transition (EMT), as well as explore the link between IL-17E and the NF-κB pathway. Experimental techniques include CCK-8, EdU, colony formation, RT-qPCR, western blotting, flow cytometry, wound-healing, transwell and immunofluorescence assay.

Results

IL-17E levels was elevated in NSCLC tissues and cells, which was related to higher TNM staging, positive lymph node metastasis and decreased tumor differentiation degree. Exogenous recombinant human IL-17E (rhIL-17E) treatment promoted cell proliferation, reduced cell apoptosis, and increased the level of Bcl-2/BAX. Moreover, it enhanced cell migration, invasion, EMT and phosphorylation levels of NF-κB p65. Inversely, knocking down endogenous IL-17E in A549 cells had the opposite effect. Blocking the NF-κB pathway with BAY-117082 reduced IL-17E expression and reversed the malignant effects induced by IL-17E on A549 cells.

Conclusion

IL-17E facilitates NSCLC progression by promoting cell proliferation and EMT via the NF-κB pathway. IL-17E could serve as a potential strategy for NSCLC treatment.