Abnormal Methylation of SF-1 Gene Promoter Region in Endometrial Cancer and Its Mechanism

Abstract

We aim to investigate the methylation status, protein expression and clinical significance of the steroidogenic factor-1(SF-1) in endometrial carcinoma (EC), and explore the effect of abnormal methylation of SF-1 on the biological behaviour of EC. Bisulfite sequencing (BSP), western blotting (WB), and immunohistochemical were used to detect the methylation status and protein expression of SF-1 in EC tissues, paracancerous tissues and normal endometrial tissues. DNA methyltransferase inhibitor 5-Aza-CdR were used to treat HEC-1-A cell lines to demethylate SF-1. After treatment, WB and qPCR were used to detect the expression of SF-1 and its downstream target genes. Cell proliferation and apoptosis were detected by the EdU fluorescent labelling method and flow cytometry between the groups. Compared with paracancerous tissues and normal endometrial tissues, the expression of SF-1 protein in EC tissues was significantly increased (P﹤0.05). The percentage of methylated cytosine in the promoter region of the SF-1 gene in EC tissues (8.2%) was significantly lower than that in paracancerous tissues by 40.9% (P<0.05). Compared with the control group, after 5-Aza-CdR treatment, the methylation level of the SF-1 gene was significantly reduced (P﹤0.05), the expressions of SF-1 and its downstream target genes were significantly increased (P <0.05), the cell proliferation was enhanced and the cell apoptosis was significantly reduced (P <0.05). In conclusion, in EC, SF-1 gene was hypomethylated and the expression of SF-1 was increased, which promotes cell proliferation and inhibits cell apoptosis. SF-1 may become a new molecular target for early diagnosis and treatment in EC.