Loss of nuclear localization of TET2 in colorectal cancer

Yuji Huang; Guanghui Wang; Zhonglin Liang; Yili Yang; Long Cui; Chen-Ying Liu

doi:10.1186/s13148-016-0176-7

Loss of nuclear localization of TET2 in colorectal cancer

Clin Epigenetics. 2016 Jan 26:8:9. doi: 10.1186/s13148-016-0176-7. eCollection 2016.

Authors

Yuji Huang^#^{1

2}, Guanghui Wang^#^{1

2}, Zhonglin Liang^{1

2}, Yili Yang^{1

2}, Long Cui^{1

2}, Chen-Ying Liu^{1

2}

Affiliations

¹ Department of colorectal and anal surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
² Shanghai Colorectal Cancer Research Centre, Shanghai, China.

^# Contributed equally.

Abstract

5-Hydroxymethylcytosine (5hmC) is lost in multiple human cancers, including colorectal cancer (CRC). Decreased ten-eleven translocation 1 (TET1) messenger RNA (mRNA), but not other two TET family members, has been observed in the colorectal cancer and is crucial for colorectal cancer initiation. Here, we show that nuclear localization of TET2 was lost in a significant portion of CRC tissues, in association with metastasis. In CRC cells, nuclear expression of TET2 were absent but not TET3. Nuclear export inhibitor can increase the 5hmC level in CRC cells, probably through regulating TET2. Our results indicate a new mechanism of TET2 dysregulation in colorectal cancer.

Keywords: 5hmC; Colorectal cancer; DNA methylation; Nuclear localization; TET2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Active Transport, Cell Nucleus / drug effects
Cell Line, Tumor
Cell Nucleus / metabolism
Colorectal Neoplasms / etiology
Colorectal Neoplasms / genetics*
DNA Methylation
DNA-Binding Proteins / genetics*
Dioxygenases
Fatty Acids, Unsaturated / pharmacology
Humans
Polymerase Chain Reaction
Proto-Oncogene Proteins / genetics*

Substances

DNA-Binding Proteins
Fatty Acids, Unsaturated
Proto-Oncogene Proteins
Dioxygenases
TET2 protein, human
leptomycin B

Grants and funding

U24 AA020801/AA/NIAAA NIH HHS/United States