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Open AccessArticle

The PRR11-SKA2 Bidirectional Transcription Unit Is Negatively Regulated by p53 through NF-Y in Lung Cancer Cells

by Yitao Wang 1,2, Huali Weng 1,2, Ying Zhang 1,2, Yinjiang Long 1,2, Yi Li 1,2, Yulong Niu 2, Fangzhou Song 1,2 and Youquan Bu 1,2,*
1
Department of Biochemistry and Molecular Biology, Chongqing Medical University, 1# Yixueyuan Road, Yuzhong District, Chongqing 400016, China
2
Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China
*
Author to whom correspondence should be addressed.
Academic Editor: Yogesh Kumar Vashist
Int. J. Mol. Sci. 2017, 18(3), 534; https://doi.org/10.3390/ijms18030534
Received: 9 January 2017 / Revised: 19 February 2017 / Accepted: 27 February 2017 / Published: 1 March 2017
(This article belongs to the Section Biochemistry)
We previously identified proline-rich protein 11 (PRR11) as a novel cancer-related gene that is implicated in the regulation of cell cycle and tumorigenesis. Our recent study demonstrated that PRR11 and its adjacent gene, kinetochore associated 2 (SKA2), constitute a classic head-to-head gene pair that is coordinately regulated by nuclear factor Y (NF-Y). In the present study, we further show that the PRR11-SKA2 bidirectional transcription unit is an indirect target of the tumor suppressor p53. A luciferase reporter assay revealed that overexpression of wild type p53, but not mutant p53, significantly represses the basal activity and NF-Y mediated transactivation of the PRR11-SKA2 bidirectional promoter. Deletion and mutation analysis of the PRR11-SKA2 promoter revealed that p53-mediated PRR11-SKA2 repression is dependent on the presence of functional NF-Y binding sites. Furthermore, a co-immunoprecipitation assay revealed that p53 associates with NF-Y in lung cancer cells, and a chromatin immunoprecipitation assay showed that p53 represses PRR11-SKA2 transcription by reducing the binding amount of NF-Y in the PRR11-SKA2 promoter region. Consistently, the ability of p53 to downregulate PRR11-SKA2 transcription was significantly attenuated upon siRNA-mediated depletion of nuclear factor Y subunit beta (NF-YB). Notably, lung cancer patients with lower expression of either PRR11 or SKA2 along with wild type p53 exhibited the best overall survival compared with others with p53 mutation and/or higher expression of either PRR11 or SKA2. Taken together, our results demonstrate that p53 negatively regulates the expression of the PRR11-SKA2 bidirectional transcription unit through NF-Y, suggesting that the inability to repress the PRR11-SKA2 bidirectional transcription unit after loss of p53 might contribute to tumorigenesis. View Full-Text
Keywords: p53; NF-Y; bidirectional promoter; PRR11; SKA2; lung cancer p53; NF-Y; bidirectional promoter; PRR11; SKA2; lung cancer
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Wang, Y.; Weng, H.; Zhang, Y.; Long, Y.; Li, Y.; Niu, Y.; Song, F.; Bu, Y. The PRR11-SKA2 Bidirectional Transcription Unit Is Negatively Regulated by p53 through NF-Y in Lung Cancer Cells. Int. J. Mol. Sci. 2017, 18, 534.

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