TET2 Regulates LncRNA-ANRIL Expression and Inhibits the Growth of Human Gastric Cancer Cells

被引:57
作者
Deng, Wei [1 ,2 ]
Wang, Jin [1 ,2 ]
Zhang, Jun [1 ,2 ]
Cai, Jun [1 ,2 ]
Bai, Zhigang [1 ,2 ]
Zhang, Zhongtao [1 ,2 ]
机构
[1] Capital Med Univ, Beijing Friendship Hosp, Dept Gen Surg, 95 Yongan Rd, Beijing 100050, Peoples R China
[2] Natl Clin Res Ctr Digest Dis, Beijing, Peoples R China
关键词
TET2; gastric cancer; lncRNA-ANRIL; apoptosis; NONCODING RNA ANRIL; MYELOID MALIGNANCIES; SIGNALING PATHWAY; LONG; COMMON; APOPTOSIS; MUTATIONS;
D O I
10.1002/iub.1490
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ten-eleven translocation (TET) family enzymes convert 5-methylcytosine to 5-hydroxymethylcytosine in DNA. However, the role of TET enzymes in human gastric cancer remains unknown. Here, we show that TET2 mRNA and protein levels are downregulated in human gastric cancer tissues when compared with normal gastric mucosa. Low expression of TET2 predicts poor overall and disease-free survival. Furthermore, we demonstrate that TET2 inhibits the proliferation and colony formation of human gastric cancer cells by using loss-of-function and gain-of-function strategies. Overexpression of TET2 induces apoptosis in human gastric cancer cells. The mechanism study shows that TET2 binds to the promoter region of the oncogenic long noncoding RNA (lncRNA-ANRIL) and regulates the expression of ANRIL and its downstream genes (INK4a, INK4b, and ARF). Finally, we demonstrate that ANRIL knockdown blocks the effects of TET2 on gastric cancer cell proliferation and colony formation. (C) 2016 IUBMB Life.
引用
收藏
页码:355 / 364
页数:10
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