GAS5 is downregulated in gastric cancer cells by promoter hypermethylation and regulates adriamycin sensitivity

Abstract

Objective: GAS5 is a tumor suppressive lncRNA that is downregulated in gastric cancer. In this study, we firstly investigated whether epigenetic regulation contributed to GAS5 downregulation and further investigated the role of GAS5 in Adriamycin (ADM) sensitivity in gastric cancer cells.

Materials and methods: GAS5 expression in 15 paired gastric cancer tissues and adjacent normal tissues and in gastric cancer cells were detected using qRT-PCR. Methylation-Specific PCR (MSP) was performed with the use of 5-AZA-dC to detect the methylation status of GAS5 promoter. SGC-7901 and SGC-7901/ADM cells were transfected for GAS5 overexpression and were further used for analysis of ADM sensitivity.

Results: GAS5 expression was significantly downregulated in gastric cancer tissues and cancer cell lines and was further downregulated in ADM resistant cells. SGC-7901/ADM cells had significantly higher level of promoter methylation than SGC-7901 cells. 5-AZA-dC treatment significantly reduced the level of methylation and restored GAS5 expression in both SGC-7901 and SGC-7901/ADM cells. SGC-7901/ADM cells with enforced GAS5 expression had significantly decreased the growth rate and increased the ratio of apoptosis after ADM treatment, suggesting that GAS5 can sensitize gastric cancer cells to ADM.

Conclusions: GAS5 is significantly downregulated in gastric cancer cells and further decreased in ADM resistant cancer cells at least partly due to promoter hypermethylation. The enforced GAS5 expression can sensitize gastric cancer cells to ADM.