Downregulation of TET1 Promotes Bladder Cancer Cell Proliferation and Invasion by Reducing DNA Hydroxymethylation of AJAP1

Frontiers in Oncology
Yi-Lin YanBing Shen

Abstract

Ten-eleven translocation 1 (TET1) is a member of methylcytosine dioxygenase, which catalyzes 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5 hmC) to promote the demethylation process. The dysregulated TET1 protein and 5 hmC level were reported to either suppress or promote carcinogenesis in a cancer type-dependent manner. Currently, the role of TET1 in the development of urinary bladder cancer (UBC) and its underlying molecular mechanisms remain unclear. Herein, we found that TET1 expression was downregulated in UBC specimens compared with normal urothelium and was inversely related to tumor stage and grade and overall survival, suggesting its negative association with UBC progression. TET1 silencing in UBC cells increased cell proliferation and invasiveness while the ectopic expression of wild-type TET1-CD, but not its enzymatic inactive mutant, reversed these effects and suppressed tumorigenicity in vivo. In addition, as a direct regulator of TET1 activity, vitamin C treatment increased 5 hmC level and inhibited the anchorage-independent growth and tumorigenicity of UBC cells. Furthermore, we found that TET1 maintained the hypomethylation in the promoter of the AJAP1 gene, which codes for adherens junction-associated pr...Continue Reading

References

May 31, 2003·Journal of Cell Science·Yoshiaki Kawano, Robert Kypta
Jan 13, 2010·Cold Spring Harbor Perspectives in Biology·Matthieu Cavey, Thomas Lecuit
Jan 14, 2012·Molecular Cancer Research : MCR·Ningjing LinDavid Cory Adamson
Mar 20, 2013·Cell Biochemistry and Biophysics·Haleh Akhavan-Niaki, Ali Akbar Samadani
Sep 21, 2013·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Jean Cadet, J Richard Wagner
May 9, 2014·Journal of Biomedical Nanotechnology·Hua-Lin FuDa-Xiang Cui
Sep 2, 2014·Molecular Medicine Reports·Hou-Gen LuGuo-Qing Chen
Mar 5, 2015·Asian Pacific Journal of Cancer Prevention : APJCP·Yi SangXiao-Bin Lv
May 16, 2015·Clinical Epigenetics·Christopher B GustafsonGaofeng Wang
Jun 23, 2015·IUBMB Life·Feng PanMingjiang Xu
Aug 31, 2016·Proceedings of the National Academy of Sciences of the United States of America·Minmin LiuPeter A Jones
Dec 29, 2016·European Urology·Geolani W DyChristina Fitzmaurice
Aug 22, 2017·Nature·Michalis AgathocleousSean J Morrison
Jun 13, 2018·Cancer Research·Charly Ryan GoodJean-Pierre J Issa
Dec 21, 2018·OncoTargets and Therapy·Wei HanChunlei Wang
Jun 7, 2019·Journal of Experimental & Clinical Cancer Research : CR·Cong XuYun Niu

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Citations

Apr 1, 2021·Free Radical Biology & Medicine·Stine Ulrik MikkelsenKirsten Grønbæk
Apr 30, 2021·Journal of Cancer Research and Clinical Oncology·Jyoti ShekhawatMithu Banerjee
Sep 8, 2021·Frontiers in Cell and Developmental Biology·Yilin YanBing Shen
Dec 3, 2021·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·Yuto MatsushitaHaruhiko Sugimura

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Methods Mentioned

BETA
transfections
electrophoresis
PCR
flow cytometry
Xenograft
xenografts
RNAseq
protein assay
Immunoprecipitation
Dot blot

Software Mentioned

DESeq2 Bioconductor
GraphPad Prism
GENEWIZ
ImageJ

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