Hypomethylation of ETS Transcription Factor Binding Sites and Upregulation of PARP1 Expression in Endometrial Cancer

Abstract

Although PARP1 promoter methylation is involved in the regulation of PARP1 expression in human keratinocyte lines and lymphoblastoid cell lines, its roles in human endometrial cancer are unknown. DNA from forty normal endometrium (NE) and fifty endometrial adenocarcinoma (EAC) tissues were analyzed by bisulfite sequencing using primers focusing on the core promoter region of PARP1. Expression levels of PARP1 were assessed by immunohistochemistry and real-time PCR. Associations between patient clinicopathological characteristics and PARP1 protein levels were assessed by Fisher’s exact test. Here, PARP1 mRNA and protein were overexpressed in EAC tissues(P<0.05). CpG sites within the ETS motif in the PARP1 promoter exhibited significant hypomethylation in EAC tissues, and there was a significant negative correlation between PARP1 mRNA levels and the number of methylated sites in both NE and EAC tissues (R2=0.262,P<0.001). Notably, PARP1 protein expression was associated with FIGO stage(P=0.026), histological grade(P=0.002), and body mass index(P=0.04). Our findings imply that PARP1 overexpression may participate in endometrial cancer progression, and abnormal hypomethylation of CpG sites within the ETS motif in the core promoter region may be responsible for PARP1 overexpression in EAC tissues.