FOXM1 promotes the progression of non-small cell lung cancer by inhibiting miR-509-5p expression via binding to the miR-509-5p promoter region

Abstract

BackgroundForkhead box M1 (FOXM1) functions as a transcription factor and is consistently overexpressed in various cancers, including non-small-cell lung-, breast-, cervical-, and colorectal cancer. Its overexpression is associated with poor prognosis in patients with non-small-cell lung cancer, although the detailed mechanisms by which FOXM1 promotes the development of non-small-cell lung cancer remain unclear. ObjectiveThe mechanism of FOXM1 in migration, invasion, apoptosis, and viability of lung cancer cells was investigated. MethodsTranswell assay, scratch test, and flow cytometry were employed to study the effects of FOXM1 on migration, invasion, and apoptosis in A549 cells. A quantitative polymerase chain reaction was used to determine the impact of FOXM1 on miR-509-5p expression in A549 cells. Dual-luciferase reporter gene assay and chromatin immunoprecipitation were adopted to investigate the molecular mechanisms of FOXM1 on miR-509-5p expression. ResultsFDI-6 (a FOXM1 inhibitor) reduced the protein abundance of FOXM1, thereby increasing the expression of miR-509-5p in A549 cells. Moreover, FDI-6 treatment significantly reduced migration, invasion, and viability of A549 cells while promoting cell apoptosis. Furthermore, miR-509-5p inhibitor obviously alleviated the biological effects of FDI-6 on A549 cells, suggesting that FOXM1 primarily exerted its cancer promoting effect by regulating miR-509-5p. Mechanistically, FOXM1 directly bound to the miR-509-5p promoter to inhibit miR-509-5p expression. ConclusionFOXM1 directly binds to the promoter region of miR-509-5p to form a negative feedback loop, thereby inhibiting miR-509-5p expression and promoting the development of non-small-cell lung cancer. This study is expected to complement research on the pathogenesis of non-small-cell lung cancer and promote the development of novel therapeutic targets for this disease.