Down-regulation of FOXO1 by DNA hypermethylation promoting the proliferation and inva-sion of nasopharyngeal carcinoma cells
Objective:To explore the molecular mechanism of abnormal expression of forkhead box O1(FOXO1)in nasopharyngeal carcinoma(NPC)and its impact on the malignant biological behavior of NPC cells.Methods:GEO dataset was used to analyze FOXO1 expression levels in NPC,and R4.2.1 software was used for gene set enrichment analysis.NPC cell lines 5-8F and HONE1 with overexpressing FOXO1(FOXO1-5-8F,Ctrl-5-8F,FOXO1 HONE1,Ctrl-HONE1)were constructed.Cell proliferation,migration,and invasion abilities were assessed through the cell counting kit-8(CCK-8)assay,scratch assay,and Transwell assay,respectively.The cell cycle was analyzed by using flow cytometry.FOXO1 DNA methylation sequencing by bisulfite gene sequencing technology was performed.Results:The expression of FOXO1 mRNA was down-regulated in NPC cells and tis-sues.Cell proliferation and migration abilities in the FOXO1 overexpression group were significantly lower than those in the control group(P＜0.05),the number of cell invasion in the blank control group was higher than that in the FOXO1 overexpression group at the same time(P＜0.05),and FOXO1 overexpression inhibited the cell cy-cle(P＜0.05).The promoter region of FOXO1 DNA in NPC tissues was observed to contain a methylation site,with a significantly higher level of methylation compared to non-cancerous tissues(P＜0.05).Conclusion:Down-regulation of FOXO1 transcription via DNA hypermethylation in NPC promotes the proliferation and inva-sion of NPC cells.FOXO1may act as a tumor suppressor gene for NPC.
万方数据
维普
