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Int. J. Mol. Sci. 2017, 18(3), 534; doi:10.3390/ijms18030534

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

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
Received: 9 January 2017 / Revised: 19 February 2017 / Accepted: 27 February 2017 / Published: 1 March 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

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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