FBXO25 promotes cell proliferation, invasion, and migration of NSCLC

Abstract

FBXO25 is a recently discovered protein that belongs to the Fbx class of the F-box family of proteins, and F-box proteins play a crucial role in tumorigenesis. However, the function of FBXO25 in cancer was not revealed so far. As measured by immunohistochemical staining, FBXO25 was highly expressed in the cytoplasm and nucleus of lung cancer samples (64.2 %, 136/212), compared with adjacent normal lung tissues (23.3 %, 7/30, p < 0.01). In addition, its expression was positively correlated with TNM staging (p < 0.001) and lymph node metastasis (p = 0.017). The overall survival of non-small-cell lung cancer (NSCLC) patients with FBXO25-positive expression (40.646 ± 1.745 months) was significantly reduced compared with those with FBXO25-negative expression (46.548 ± 2.176 months, p = 0.023). Consistently, we found that the proliferation, invasion, and migration capacity of A549 cells transfected with FBXO25 were significantly greater than those of control cells, while interference of FBXO25 could significantly inhibit cell proliferation, invasion, and migration in H1299 cells. Furthermore, we demonstrated that FBXO25 could regulate the expression of β-catenin, YAP, some cyclins, and matrix metalloproteinases (MMPs). Collectively, these results indicate that FBXO25 may promote the tumorigenicity of lung cancer cells and might serve as a novel therapeutic target of NSCLC.

Keywords: FBXO25; Invasion; Migration; NSCLC; Proliferation.