Oncotarget

Research Papers:

Tianshengyuan-1 (TSY-1) regulates cellular Telomerase activity by methylation of TERT promoter

Weibo Yu, Xiaotian Qin, Yusheng Jin, Yawei Li, Chintda Santiskulvong, Victor Vu, Gang Zeng, Zuofeng Zhang, Michelle Chow and Jianyu Rao _

PDF  |  HTML  |  How to cite

Oncotarget. 2017; 8:7977-7988. https://doi.org/10.18632/oncotarget.13939

Metrics: PDF 2745 views  |   HTML 3704 views  |   ?  


Abstract

Weibo Yu1, Xiaotian Qin2, Yusheng Jin1, Yawei Li2, Chintda Santiskulvong3, Victor Vu1, Gang Zeng4,5, Zuofeng Zhang6, Michelle Chow1, Jianyu Rao1,5

1Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

2Beijing Boyuantaihe Biological Technology Co., Ltd., Beijing, China

3Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA

4Department of Urology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

5Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, USA

6Department of Epidemiology, School of Public Health, University of California at Los Angeles, Los Angeles, CA, USA

Correspondence to:

Jianyu Rao, email: [email protected]

Keywords: TSY-1, hematopoietic cells, Telomerase, TERT, methylation

Received: September 08, 2016     Accepted: November 24, 2016     Published: December 15, 2016

ABSTRACT

Telomere and Telomerase have recently been explored as anti-aging and anti-cancer drug targets with only limited success. Previously we showed that the Chinese herbal medicine Tianshengyuan-1 (TSY-1), an agent used to treat bone marrow deficiency, has a profound effect on stimulating Telomerase activity in hematopoietic cells. Here, the mechanism of TSY-1 on cellular Telomerase activity was further investigated using HL60, a promyelocytic leukemia cell line, normal peripheral blood mononuclear cells, and CD34+ hematopoietic stem cells derived from umbilical cord blood. TSY-1 increases Telomerase activity in normal peripheral blood mononuclear cells and CD34+ hematopoietic stem cells with innately low Telomerase activity but decreases Telomerase activity in HL60 cells with high intrinsic Telomerase activity, both in a dose-response manner. Gene profiling analysis identified Telomerase reverse transcriptase (TERT) as the potential target gene associated with the TSY-1 effect, which was verified by both RT-PCR and western blot analysis. The β-galactosidase reporter staining assay showed that the effect of TSY-1 on Telomerase activity correlates with cell senescence. TSY-1 induced hypomethylation within TERT core promoter in HL60 cells but induced hypermethylation within TERT core promoter in normal peripheral blood mononuclear cells and CD34+ hematopoietic stem cells. TSY-1 appears to affect the Telomerase activity in different cell lines differently and the effect is associated with TERT expression, possibly via the methylation of TERT promoter.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 13939