ISG20L2 as a driver in the proliferation and invasion of lung adenocarcinoma via NKX2-1 regulation

Background: Interferon-stimulated 20-kDa exonuclease-like 2 (ISG20L2) is a gene that shows variable expression levels in lung adenocarcinoma (LUAD). Despite this, its role and expression in LUAD have not been well characterized. This study focused on analyzing the expression of ISG20L2 in LUAD, its association with patient prognosis, and its potential regulatory influence on NK2 homeobox 1 (NKX2-1) in LUAD cells. Methods: We used The Cancer Genome Atlas (TCGA) database and immunohistochemistry to assess the expression of ISG20L2. Kaplan-Meier survival analysis was employed to determine the relationship between ISG20L2 expression and prognosis in patients with LUAD. The diagnostic potential of ISG20L2 in LUAD was evaluated through receiving operating characteristic curve analysis. The association between ISG20L2 expression and clinicopathological features was analyzed with the Fisher exact test. Overexpression and depletion studies of ISG20L2 were performed via transient transfection. The biological functions of ISG20L2 in A549 cells, such as cell proliferation, apoptosis, migration, and invasion, were examined via Cell Counting Kit-8 (CCK-8), flow cytometry, and Transwell assays. Bioinformatics analysis suggested a link between ISG20L2 and NKX2-1, which was subsequently confirmed through cytological experiments. Results: Our results demonstrated that ISG20L2 was overexpressed in LUAD, and this overexpression was significantly correlated with poor prognosis. In vitro experiments further supported a positive association between ISG20L2 expression and the proliferative, migratory, and invasive capabilities in A549 cells, with no notable effect on apoptosis. Functional assays confirmed that ISG20L2 enhanced A549 cell proliferation and invasion by modulating NKX2-1. Conclusions: ISG20L2 promotes LUAD progression via NKX2-1 regulation, implying the potential of the ISG20L2/NKX2-1 axis as a candidate biomarker and therapeutic target in LUAD.