TY - JOUR A2 - Li, Xiaohong AU - Du, Xiaoxiao AU - Wu, Lingyan AU - Ur Rahman, Muhammad Saif AU - Teng, Xiaodong AU - Teng, Lisong AU - Ye, Jingjia AU - Cao, Jiang PY - 2019 DA - 2019/08/28 TI - Promoter Hypomethylation Is Responsible for Upregulated Expression of HAI-1 in Hepatocellular Carcinoma SP - 9175215 VL - 2019 AB - An upregulated expression of hepatocyte growth factor activator inhibitor type 1 (HAI-1) in hepatocellular carcinomas (HCC) associates with poor prognosis, but the underlying mechanism for expression regulation has not been elucidated. HAI-1 was expressed in HCC cell line Hep3B cells at a high level but absent or has a low level in other HCC cell lines HepG2 and SMMC7721 and immortal normal liver cell line L02 at transcriptional and translational levels, respectively. A dual-luciferase reporter assay showed that transcriptional activity of HAI-1 in the promoter region (-452 bp to -280 bp from the mRNA start site) was strongly enhanced in Hep3B and SMMC7721. Bisulfite genomic sequencing results of the HAI-1 promoter region showed an inverse correlation between levels of promoter methylation and expression in HCC cells. The expression level of HAI-1 in SMMC7721, HepG2, and L02 cells was elevated after 5-Aza-2-deoxycytidine treatment. Hypomethylation of the HAI-1 promoter region contributed to the elevated HAI-1 expression in HCC tissues. In addition, the hypomethylation of the HAI-1 promoter region correlated with poor differentiation status of HCC tissues. Our findings indicate that promoter hypomethylation is an important mechanism for aberrant HAI-1 expression regulation in HCC. SN - 0278-0240 UR - https://doi.org/10.1155/2019/9175215 DO - 10.1155/2019/9175215 JF - Disease Markers PB - Hindawi KW - ER -