Klotho is silenced through promoter hypermethylation in gastric cancer
Liangjing Wang, Xian Wang, Xiaojia Wang, Pan Jie, Haiqi Lu, Shengjie Zhang, Xiaoying Lin, Emily Ky Lam, Yan Cui, Jun Yu, Hongchuan Jin, Liangjing Wang, Xian Wang, Xiaojia Wang, Pan Jie, Haiqi Lu, Shengjie Zhang, Xiaoying Lin, Emily Ky Lam, Yan Cui, Jun Yu, Hongchuan Jin
Abstract
As one of major epigenetic changes to inactivate tumor suppressor genes in human carcinogenesis, promoter hypermethylation was proposed as a marker to define novel tumor suppressor genes and predict the prognosis of cancer patients. In the present study, we found KL (klotho) as a novel tumor suppressor gene silenced through promoter hypermethylation in gastric cancer, the second leading cause of cancer death worldwide. KL expression was downregulated in primary gastric carcinoma tissues (n=22, p<0.05) and all of gastric cancer cells lines examined. Ectopic expression of KL inhibited the growth of gastric cancer cells partially through the induction of apoptosis, demonstrating a tumor suppressive role of KL in gastric cancer. Demethylation with 5-aza-2'-deoxycytidine (Aza) increased KL expression and KL promoter was hypermethylated in gastric cancer cell lines as well as some of primary gastric carcinoma tissues (47/99) but none of normal gastric tissues. Importantly, promoter methylation of KL was significantly associated with the poor outcome of gastric cancer patients (p=0.025, Log-rank test), highlighting the relevance of epigenetic inactivation of KL in gastric carcinogenesis. As a summary, we found that KL is a novel tumor suppressor gene epigenetically inactivated in gastric cancer and promoter methylation of KL could be used to predict the prognosis of gastric cancer patients.
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Source: PubMed