TET1 exerts its tumour suppressor function by regulating autophagy in glioma cells
Authors: Li Yu
Yan Ding
Shi Wen Guo
Rui Fu
Jie Luo
Cheng Lin Li
Dong Sheng Li
Journal: Bioscience Reports (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CRISPR/Caspase-9; TET1; autophagy; glioma; methylation.
Affiliations: Department of neurosurgery, affiliated Taihe hospital of Xi’an Jiaotong University Health Science Center, Shiyan, Hubei, China, Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, China

Abstract:  DNA methylation and demethylation play a critical role in the regulation of the molecular pathogenesis of gliomas. Tet methylcytosine dioxygenase 1 (TET1) catalyses the sequential oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine, (5hmC) leading to eventual DNA demethylation. It has been reported that TET1 is a tumour suppressor in several cancers. However, whether TET1 plays a role in glioma development is largely unclear. Different glioma specimens and corresponding normal controls were collected to analyse the expression of TET1. At the same time, TET1 of glioma U251 cells was knocked down 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-tumour normal tissues, and the concentration of TET1 is negatively correlated with the glioma WHO classification. When TET1 gene in glioma U251 cells was knocked down by CRISPR/Caspase-9 system, the proliferation and invasive ability of U251 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.However, when TET1 was overexpressed in U251 cells, the level of autophagy incraesed. Furthermore, bafilomycin A1 (Baf-A1) but not 3-methyladenine (3-MA) could decrease the autophagy level of TET1-/- U251 cells as the wild-type controls. It suggests that the tumour suppressor effect of TET1 seems to be mediated by regulating the level of autophagy, and the regulation of TET1 on autophagy is at an early stage. 

Retracted: No

PubPeer comments:
 The 3rd author of this paper is Philip Baker. His affiliation is listed as u201cKeele University School of Medicineu201d. The paper was submitted on 20th August 2013. However, it appears that in August 2013, Philip Baker was based at the Gravida Centre and Liggins Institute at the University of Auckland. Please see here: http: www.gravida.org.nz news-and-events news funding-decision-unexpected http: www.liggins.auckland.ac.nz en about news news-2013 2013 07 11 Long-research-journey-to-clinical-trial.html Could the authors please explain why an incorrect affiliation appears to have been listed for Philip Baker? Could the authors also confirm if they have published their standard operating procedure (SOP) for sample collection for this trial, because this was flagged as a problem in another study by the Baker group: u201cHas their SOP been approved, validated, and or published in their new research setting after the closures of their laboratory first in the University of Alberta, Canada and then the University of Auckland, New Zealand?u201d Please see here for further details: https: pubpeer.com publications 478CCB141205AA26650AF96C23251F ,