Research Papers:

Overexpression of KLF4 promotes cell senescence through microRNA-203-survivin-p21 pathway

Qing Xu, Mei Liu, Ju Zhang, Liyan Xue, Guo Zhang, Chenfei Hu, Zaozao Wang, Shun He, Lechuang Chen, Kai Ma, Xianghe Liu, Yahui Zhao, Ning Lv, Shufang Liang, Hongxia Zhu and Ningzhi Xu _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2016; 7:60290-60302. https://doi.org/10.18632/oncotarget.11200

Metrics: PDF 3299 views  |   HTML 4119 views  |   ?  


Qing Xu1, Mei Liu1, Ju Zhang2, Liyan Xue3, Guo Zhang1, Chenfei Hu1, Zaozao Wang1, Shun He1, Lechuang Chen1, Kai Ma1, Xianghe Liu1, Yahui Zhao1, Ning Lv3, Shufang Liang4, Hongxia Zhu1, Ningzhi Xu1,4

1Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

2Division of Proteomics, Beijing Institute of Genomics, Chinese Academy of Science, Beijing, China

3Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

4State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, P. R. China

Correspondence to:

Hongxia Zhu, email: [email protected]

Ningzhi Xu, email: [email protected]

Keywords: KLF4, p21, survivin, miR-203, senescence

Received: November 20, 2015     Accepted: July 26, 2016     Published: August 11, 2016


Krüppel-like factor 4 (KLF4) is a transcription factor and functions as a tumor suppressor or tumor promoter in different cancer types. KLF4 regulates many gene expression, thus affects the process of cell proliferation, differentiation, and apoptosis. Recently, KLF4 was reported to induce senescence during the generation of induced pluripotent stem (iPS) cells, but the exact mechanism is still unclear. In this study, we constructed two doxycycline-inducing KLF4 cell models, and demonstrated overexpression of KLF4 could promote cell senescence, detected by senescence-associated β-galactosidase activity assay. Then we confirmed that p21, a key effector of senescence, was directly induced by KLF4. KLF4 could also inhibit survivin, which could indirectly induce p21. By miRNA microarray, we found a series of miRNAs regulated by KLF4 and involved in senescence. We demonstrated that KLF4 could upregulate miR-203, and miR-203 contributed to senescence through miR-203-survivin-p21 pathway. Our results suggest that KLF4 could promote cell senescence through a complex network: miR-203, survivin, and p21, which were all regulated by overexpression of KLF4 and contributed to cell senescence.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 11200