The Role Of FOXM1 In Esophageal Squamous Cell Carcinoma Cell Proliferation And Migration

Esophageal carcinoma is one of the most malignant cancers. There are two major histological subtypes of esophageal cancer, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EADC). Although EADC is one of the most common tumors in western countries, ESCC is still the most predominant histological subtype of esophageal cancer in Asian, especially in China. Despite significant advances in surgery and adjuvant chemoradiotherapy, the prognosis of the patients with this cancer still remains poor.Forkhead box M1 (FOXM1), a transcription factor of the Forkhead family, is one of the key positive regulators of the cell cycle. The FOXM1 transcription factor is crucial for G1/S and G2/M cell cycle phase progression and mitotic spindle integrity. It has been reported that the FOXM1 is over expressed in some human malignancies, such as lung cancer, hepatocellular carcinoma, prostate cancer, primary breast cancer and so on. However, the role of FOXM1 in ESCC development and progression remains unknown.To investigate the effects of FOXM1 on ESCC proliferation and migration, the expression level of FOXM1 was down-regulated or up-regulated in ESCC, TE-1. 3 RNAi plasmids (pLKO.1-FOXM1 shRNA 1, pLKO.1-FOXM1 shRNA 2, and pLKO.1-FOXM1 shRNA 3) and 2 recombinant plasmids (iduet011a-FOXM1, iduet011a-N-TAP-FOXM1) were constructed and transfected into HEK293T cells with pCMV-DR8.2, pCMV-VSV-G, generating lentiviral particles, and then infected the target cell. Cells that stably express shRNA were selected by puromycin. FOXM1 expression was measured by Western blot. The effect of FOXM1 shRNA on cell proliferation and cell migration was examined by methyl thiazolyl tetrazolium (MTT) and wound-healing assay.We found that RNA interference could suppress the FOXM1 expression in TE-1 cells, but the inhibitory effects of different plasmids varied. pLKO.1-FOXM1 shRNA 2 group had the most best effect. As compared to pLKO.1-scramble group, the pLKO.1-FOXM1 shRNA groups showed lower proliferation at 48 and 72h. Furthermore, shRNA mediated knockdown of FOXM1 in TE-1 cells inhibited the cell migration.Down-regulation of FOXM1 could inhibit ESCC proliferation and migration in vitro, which provides an experimental evidence for further investigating its role in the development of ESCC in vivo.