Forkhead box N1 inhibits the progression of non-small cell lung cancer and serves as a tumor suppressor

摘要

Forkhead box N1 (FOXN1) belongs to the FOX family of transcription factors, which comprises a diverse group of winged-helix proteins. FOXN1 is a ubiquitously expressed member that has been implicated in the embryo development, metabolism, aging and cancer. However, little is known regarding the role of FOXN1 in non-small cell lung cancer (NSCLC). The aim of the study was to investigate the function of FOXN1 in NSCLC and examine the relevant mechanism. In the present study, using reverse transcription-quantitative polymerase chain reaction, western blotting, transwell assay, MTT assay, luciferase report assy, it was identified that knockdown of FOXN1 increased the proliferation of A549 and H1299 cells, while overexpression of FOXN1 evidently suppressed the cell growth. A Transwell assay was used to determine the relative cell invasion ability, and it was observed that the invading cells were markedly decreased in the FOXN1 overexpression groups; by contrast, reduced expression of FOXN1 demonstrated the potential to promote cell invasion. Furthermore, lower expression of FOXN1 was observed in NSCLC tissues and cell lines as compared with the adjacent non-tumor tissues or human bronchial epithelial cells, respectively. A higher level of FOXN1 was associated with a better prognosis of NSCLC patients. Quantitative chromatin immunoprecipitation analysis and luciferase reporter gene assays revealed that enhancer of zeste homolog 2 (EZH2) and β-catenin were two target genes of FOXN1. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis indicated that FOXN1 suppressed the expression levels of these target genes at the transcriptional level. In conclusion, the present study demonstrated that FOXN1 served major roles in NSCLC proliferation and invasion by directly repressing EZH2 and β-catenin, which suggested that FOXN1 may function as a tumor suppressor in NSCLC.