Zhang N, Wang A-Y, Wang X-K, Sun X-M, Xue H-Z
Thoracic Cancer Center, People's Hospital of Zhengzhou University (Henan 1Provincial People's Hospital, Zhengzhou, Henan, China.
Eur Rev Med Pharmacol Sci. 2016 Jul;20(15):3199-205.
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.
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.
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.
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.
GAS5是一种在胃癌中表达下调的肿瘤抑制性长链非编码RNA。在本研究中，我们首先探究表观遗传调控是否导致GAS5表达下调，并进一步研究GAS5在胃癌细胞对阿霉素（ADM）敏感性中的作用。
采用qRT-PCR检测15对胃癌组织及癌旁正常组织以及胃癌细胞中GAS5的表达。使用5-氮杂-2'-脱氧胞苷进行甲基化特异性PCR（MSP）以检测GAS5启动子的甲基化状态。对SGC-7901和SGC-7901/ADM细胞进行GAS5过表达转染，并进一步用于分析ADM敏感性。
GAS5在胃癌组织和癌细胞系中表达显著下调，且在阿霉素耐药细胞中进一步下调。SGC-7901/ADM细胞的启动子甲基化水平显著高于SGC-7901细胞。5-氮杂-2'-脱氧胞苷处理显著降低了甲基化水平，并恢复了SGC-7901和SGC-7901/ADM细胞中GAS5的表达。GAS5过表达的SGC-7901/ADM细胞在阿霉素处理后生长速率显著降低，凋亡比例增加，表明GAS5可使胃癌细胞对阿霉素敏感。
GAS5在胃癌细胞中显著下调，且在阿霉素耐药癌细胞中进一步降低，至少部分原因是启动子高甲基化。过表达GAS5可使胃癌细胞对阿霉素敏感。
