Research Papers:

TET1 inhibits cell proliferation by inducing RASSF5 expression

Bo-Tai Li, Chao Yu, Ying Xu, Sheng-Bing Liu, Heng-Yu Fan and Wei-Wei Pan _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2017; 8:86395-86409. https://doi.org/10.18632/oncotarget.21189

Metrics: PDF 2628 views  |   HTML 2542 views  |   ?  


Bo-Tai Li2, Chao Yu2, Ying Xu1, Sheng-Bing Liu1, Heng-Yu Fan2 and Wei-Wei Pan1

1Department of Cell Biology, College of Medicine, Jiaxing University, Jiaxing 314001, China

2Life Sciences Institute, Zhejiang University, Hangzhou 301158, China

Correspondence to:

Wei-Wei Pan, email: [email protected]

Heng-Yu Fan, email: [email protected]

Keywords: ovarian cancer, TET1, RASSF5, proliferation, DNA methylation

Received: May 07, 2017     Accepted: August 23, 2017     Published: September 23, 2017


Tet methylcytosine dioxygenases (TETs) catalyze the oxidative reactions of 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). However, TET1 roles in ovarian cancer cell growth are unknown. Here, we show that ectopic expression of TET1 increased 5hmC levels, and inhibited proliferation and colony formation in ovarian cancer cell lines. Furthermore, in vitro and in vivo functional studies demonstrated that TET1 overexpression is necessary for the suppression of ovarian cancer growth, whereas depletion of TET1 expression had the opposite effect. Furthermore, the results of RNA-seq and qRT-PCR analyses identified a tumor suppressor, Ras association domain family member 5 (RASSF5), as the key downstream target of TET1. TET1 promotes RASSF5 expression by demethylating a CpG site within RASSF5 promoter. Up-regulated RASSF5 expression leads to the suppression of ovarian cancer cells growth. Additionally, we demonstrated that inhibition of CUL4-DDB1 ubiquitin ligase complex decrease 5hmC levels in ovarian cancer cells. These results provide new insights into the understanding of how ovarian cancers develop and grow, and identify TET1 as a key player in this process.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 21189