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. © 2016 IUBMB Life 68(5):355-364, 2016.
Keywords: TET2; apoptosis; gastric cancer; lncRNA-ANRIL.
© 2016 International Union of Biochemistry and Molecular Biology.