Aberrant expression of the candidate tumor suppressor gene DAL-1 due to hypermethylation in gastric cancer.
Aberrant expression of the candidate tumor suppressor gene DAL-1 due to hypermethylation in gastric cancer.
复制标题
胃癌中由于高甲基化导致候选抑癌基因 DAL-1 的异常表达。
DOI：
10.1038/srep21755
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发表时间：
2016-02-29
影响因子：
4.6
通讯作者：
Yu J
中科院分区：
文献类型：
--
作者：
Wang H;Xu M;Cui X;Liu Y;Zhang Y;Sui Y;Wang D;Peng L;Wang D;Yu J
通过等位基因杂合性缺失（洛）分型，我们先前在散发性胃癌（GC）中发现了一个包含候选抑癌基因DAL-1的18 p11.3缺失区。DAL-1在GC中的表达和功能尚不清楚。在这里，我们证明了DAL-1 mRNA和蛋白表达的缺失或显著降低与原发性GC组织和GC细胞系中DAL-1启动子的CpG超甲基化高度相关。此外，在GC细胞中也观察到异常的DAL-1亚细胞定位。外源性DAL-1能有效抑制胃癌细胞的增殖、迁移、侵袭和上皮间质转化（EMT），并能促进胃癌细胞的凋亡。当内源性DAL-1在GC HGC-27细胞中被敲低时，细胞表现出高度侵袭性。总之，这些发现提供了坚实的证据，DAL-1的异常表达的启动子区域的超甲基化的结果在肿瘤抑制基因的行为，发挥重要作用的恶性GC。了解DAL-1在胃癌分子发病机制中的作用，DAL-1可能成为胃癌分子诊断和评价的潜在生物标志物。
By allelotyping for loss of heterozygosity (LOH), we previously identified a deletion region that harbors the candidate tumor suppressor gene DAL-1 at 18p11.3 in sporadic gastric cancers (GCs). The expression and function of DAL-1 in GCs remained unclear. Here, we demonstrated that the absence of or notable decreases in the expression of DAL-1 mRNA and protein was highly correlated with CpG hypermethylation of the DAL-1 promoter in primary GC tissues and in GC cell lines. Furthermore, abnormal DAL-1 subcellular localization was also observed in GC cells. Exogenous DAL-1 effectively inhibited cancer cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT); exogenous DAL-1 also promoted apoptosis in GC AGS cells. When endogenous DAL-1 was knocked down in GC HGC-27 cells, the cells appeared highly aggressive. Taken together, these findings provide solid evidence that aberrant expression of DAL-1 by hypermethylation in the promoter region results in tumor suppressor gene behavior that plays important roles in the malignancy of GCs. Understanding the role of it played in the molecular pathogenesis of GC, DAL-1 might be a potential biomarker for molecular diagnosis and evaluation of the GC.