NEIL3 Mediates Lung Cancer Progression and Modulates PI3K/AKT/mTOR Signaling: A Potential Therapeutic Target.

Background: Nei endonuclease VIII-like 3 (NEIL3) is widely involved in pathophysiological processes of the body; however, its role in lung cancer has not been conclusively determined. Objective: This study is aimed at exploring the role of NEIL3 in lung cancer. Methods: The public data used in this study were downloaded from The Cancer Genome Atlas (TCGA) database. "Limma" in R was used for the analysis of differentially expressed genes. Clinical correlations and prognostic analyses were performed using the survival package in R. The proliferative abilities of lung cancer cells were evaluated by the CCK8 and colony formation assays while their invasive and migration abilities were assessed by the transwell and wound healing assays. Quantitative real-time PCR (qRT-PCR) and western blot analyses were utilized to detect RNA and protein levels. Biological differences between groups were determined by gene set enrichment analysis (GSEA). Tumor Immune Dysfunction and Exclusion (TIDE) as well as Genomics of Drug Sensitivity in Cancer (GDSC) was used for immunotherapeutic and chemotherapeutic sensitivity analyses. Results: NEIL3 was upregulated in NSCLC tissues and cell lines, implying that it is involved in lung cancer initiation and progression. Clinical correlation and prognostic analyses showed that NEIL3 was associated with worse clinical features (stage and T and N classifications) and poor prognostic outcomes. Conclusion: In general, NEIL3 mediates NSCLC progression and affects sensitivity to immunotherapy and chemotherapy; therefore, it is a potential molecular target for treatment.