Knockdown of FOXM1 suppresses cell growth and metastasis in human laryngeal cancer via the AKT signaling pathway.

OBJECTIVE: This study aims to investigate the potential regulatory effect of forkhead box M1 (FOXM1) on laryngeal carcinoma (LC) and the underlying mechanisms. PATIENTS AND METHODS: Tumor tissues were obtained from 80 patients diagnosed with LC in our hospital. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot analysis were used to detect the expression levels of FOXM1 in LC tissues and cell lines. Transfection of small interfering RNA (si-RNA) was conducted to knockdown the expression level of FOXM1. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay and cell colony assay were conducted to measure the changes in cell proliferation capacity influenced by FOXM1. Finally, invasion and migration ability was evaluated by the transwell assay. RESULTS: FOXM1 was found upregulated in LC tissues and cells. Transfection of FOXM1 siRNA in LC cells successfully inhibited the expression of FOXM1. The knockdown of FOXM1 resulted in reduced proliferation, invasion, and migration of LC cells. Further studies indicated that the knockdown of FOXM1 suppressed the ratio of p-AKT/AKT. Besides, the impaired proliferation, invasion, and migration of LC cells induced by FOXM1 knockdown could be counteracted by application of the AKT activator Sc79. CONCLUSIONS: The present work demonstrated that the knockdown of FOXM1 suppressed the proliferation, invasion, and migration of LC cells by the AKT signaling pathway.

Knockdown of FOXM1 inhibits activation of keloid fibroblasts and extracellular matrix production via inhibition of TGF-ß1/Smad pathway.

Keloid is characterized by overactive fibroblasts. Forkhead box M1 (FOXM1) is transcription factor that plays important roles in the progression of fibrosis. However, the role of FOXM1 in keloid has not been elucidated. In the present study, we examined the expression levels of FOXM1 in clinical keloid tissue specimens and primary keloid fibroblasts (KFs). The results showed that FOXM1 levels were significantly increased in both keloid tissues and KFs. To further investigate the biological functions of FOXM1, FOXM1 was knocked down in KFs by transfection with small interfering RNA targeting FOXM1 (si-FOXM1). Knockdown of FOXM1 inhibited transforming growth factor-ß1 (TGF-ß1)-induced cell proliferation and migration of KFs. Besides, the increased expressions of collagen (coll I), connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) in TGF-ß1-induced KFs were suppressed by si-FOXM1 transfection. Furthermore, TGF-ß1-induced increase in p-Smad2 and p-Smad3 expressions was attenuated by FOXM1 knockdown. These data indicated that knockdown of FOXM1 inhibited TGF-ß1-induced KFs activation and extracellular matrix (ECM) accumulation, which was attributed to the inhibition of TGF-ß1/Smad pathway.