Decrease in Lymphoid Specific Helicase and 5-hydroxymethylcytosine Is Associated with Metastasis and Genome Instability

Release time:2020-07-13

Impact Factor:8.579

Affiliation of Author(s):中南大学

Journal:Theranostics

Key Words:5-hmC; LSH; TET2; genome instability.; satellites

Abstract:DNA methylation is an important epigenetic modification as a hallmark in cancer. Conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) by ten-eleven translocation (TET) family enzymes plays an important biological role in embryonic stem cells, development, aging and disease. Lymphoid specific helicase (LSH), a chromatin remodeling factor, is regarded as a reader of 5-hmC. Recent reports show that the level of 5-hmC is altered in various types of cancers. However, the change in 5-hmC levels in cancer and associated metastasis is not well defined. We report that the level of 5-hmC was decreased in metastatic tissues of nasopharyngeal carcinoma, breast cancer, and colon cancer relative to that in non-metastasis tumor tissues. Furthermore, our data show that TET2, but not TET3, interacted with LSH, whereas LSH increased TET2 expression through silencing miR-26b-5p and miR-29c-5p. Finally, LSH promoted genome stability by silencing satellite expression by affecting 5-hmC levels in pericentromeric satellite repeats, and LSH was resistant to cisplatin-induced DNA damage. Our data indicate that 5-hmC might serve as a metastasis marker for cancer and that the decreased expression of LSH is likely one of the mechanisms of genome instability underlying 5-hmC loss in cancer.

Co-author:Ling Chen, Weiwei Lai, Bin Yan, Yiqun Jiang, Desheng Xiao, Sichuan Xi, Ya Cao, Shuang Liu, Yan Cheng

First Author:Jiantao Jia, Ying Shi

Indexed by:Journal paper

Correspondence Author:Yongguang Tao

Volume:7(16)

Page Number:3920-3932

Translation or Not:no

Date of Publication:2017-09-05

Included Journals:SCI