Theranostics 2017; 7(16):3920-3932. doi:10.7150/thno.21389
Decrease in Lymphoid Specific Helicase and 5-hydroxymethylcytosine Is Associated with Metastasis and Genome Instability
1. Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Xiangya Hospital, Central South University, Changsha, Hunan, 410008 China;
2. Department of Pathophysiology, Changzhi Medical College, Changzhi, Shanxi, 046000 China;
3. Cancer Research Institute, Central South University, Changsha, Hunan, 410078 China;
4. Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, 410008 China;
5. Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410078 China;
6. Thoracic Surgery Section, Thoracic and GI Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA;
7. Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410078 China.
* equal contribution
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.
Keywords: LSH, 5-hmC, TET2, satellites, genome instability.
Jia J, Shi Y, Chen L, Lai W, Yan B, Jiang Y, Xiao D, Xi S, Cao Y, Liu S, Cheng Y, Tao Y. Decrease in Lymphoid Specific Helicase and 5-hydroxymethylcytosine Is Associated with Metastasis and Genome Instability. Theranostics 2017; 7(16):3920-3932. doi:10.7150/thno.21389. Available from http://www.thno.org/v07p3920.htm