A p53/CPEB2 negative feedback loop regulates renal cancer cell proliferation and migration

Jiehui Di; Guang Zhao; Hui Wang; Yaoyao Wu; Zhongjun Zhao; Bao Zhu; Yanping Zhang; Junnian Zheng; Yong Liu; Ying Hu

doi:10.1016/j.jgg.2021.05.011

Volume 48 Issue 7

Jul. 2021

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Article Navigation > Journal of Genetics and Genomics > 2021 > 48(7): 606-617

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A p53/CPEB2 negative feedback loop regulates renal cancer cell proliferation and migration

doi: 10.1016/j.jgg.2021.05.011

Jiehui Di^a,b,c,d,
Guang Zhao^b,c,d,
Hui Wang^b,c,d,
Yaoyao Wu^b,c,d,
Zhongjun Zhao^b,c,d,
Bao Zhu^b,c,d,
Yanping Zhang^e,
Junnian Zheng^b,c,d,
Yong Liu^b,c,d,
Ying Hu^a,f

a School of Life Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang 150001, China;
b Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China;
c Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, China;
d Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China;
e Department of Radiation and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, 450 West Drive, Chapel Hill, NC 27599-7461, USA;
f Shenzhen Graduate School of Harbin Institute of Technology, Shenzhen 518055, China

Funds:

We thank all the members of Hu's and Liu's laboratory for their discussion and technical support of this work. This study was supported by grants from the National Natural Science Foundation of China (81972377, 82025027, 31301131 and 81972723), the Science and Technology Project of Xuzhou (KC19064), the Social Development Project of Jiangsu Province (BE2019644), and the Natural Science Foundation of the Jiangsu Higher Education Institutions (18KJA320012).

Received Date: 2021-01-06
Accepted Date: 2021-05-29
Rev Recd Date: 2021-05-25
Publish Date: 2021-07-20

Abstract

Abstract

The tumor suppressor p53 transactivates the expression of multiple genes to exert its multifaceted functions and ultimately maintains genome stability. Thus, cancer cells develop various mechanisms to diminish p53 expression and bypass the cell cycle checkpoint. In this study, we identified the gene encoding RNA-binding protein cytoplasmic polyadenylation element-binding protein 2 (CPEB2) as a p53 target. In turn, CPEB2 decreases p53 messenger RNA stability and translation to fine-tune p53 level. Specifically, we showed that CPEB2 binds the cytoplasmic polyadenylation elements in the p53 3'-untranslated region, and the RNA recognition motif and zinc finger (ZF) domains of CPEB2 are required for this binding. Furthermore, we found that CPEB2 was upregulated in renal cancer tissues and promotes the renal cancer cell proliferation and migration. The oncogenic effect of CPEB2 is partially dependent on negative feedback regulation of p53. Overall, we identify a novel regulatory feedback loop between p53 and CPEB2 and demonstrate that CPEB2 promotes tumor progression by inactivating p53, suggesting that CPEB2 is a potential therapeutic target in human renal cancer.
- p53,
- CPEB2,
- Cell proliferation,
- Migration,
- Renal cancer

These authors contributed equally to this work

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References(36)

References

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