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Bioscience reports

TET1 exerts its tumor suppressor function by regulating autophagy in glioma cells.


PMID 28341638

Abstract

DNA methylation and demethylation play a critical role in the regulation of the molecular pathogenesis of gliomas. TET1 catalyzes the sequential oxidation of 5-methylcytosine to 5-hydroxymethyl-cytosine, leading to eventual DNA demethylation. It has reported that TET1 is a tumor suppressor in several cancers. However, whether TET1 play a role in glioma development is largely unclear. Different glioma specimens and corresponding normal contols were collected to analysis the expression of TET1. At the same, TET1 of glioma U251 cells was knockdown or overexpressed to observe its effect on glioma cell proliferation and invasion as well as autophagy level. Here we reported that the expression of TET1 in glioma tissue was significantly lower than the corresponding non-tumor normal tissues, and the concentration of TET1 is negatively correlated with the glioma WHO classification. When TET1 gene in glioma U251 cells were knockdown by CRISPR/Caspase-9 system, the proliferation and invasive ability of U251 were both increased remarkably. But when TET1 was overexpressed in U251 cells, the proliferation and invasion were impaired. Following the down expression of TET1, the level of autophagy in U251 cells decreased accordingly. On the contrary, when TET1 was forced expression, the autophagy was increased. Furthermore, Baf-A1 but not 3-MA could decrease the autophagy level of TET1(-/-) U251 cells as the wild type controls. It suggested that the tumor suppressor effect of TET1 seems to be mediated by regulating the level of autophagy, and the regulation of TET1 on autophagy is at the early stage.