BMB Reports 2019; 52(2): 157-162  https://doi.org/10.5483/BMBRep.2019.52.2.207
PRR11 and SKA2 gene pair is overexpressed and regulated by p53 in breast cancer
Yitao Wang1, Chunxue Zhang2, Li Mai3, Yulong Niu1, Yingxiong Wang4 and Youquan Bu1,*

1Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, 2Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu 610000, 3Department of Clinical Laboratory, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, 4Laboratory of Reproductive Biology, School of Public Health, Chongqing Medical University, Chongqing 400016, China

Correspondence to: Tel: +86-23-68485991; Fax: +86-23-68485991; E-mail: buyqcn@cqmu.edu.cn
Received: September 7, 2018; Revised: November 2, 2018; Accepted: December 31, 2018; Published online: February 28, 2019.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

cc This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Our previous study found that two novel cancer-related genes, PRR11 and SKA2, constituted a classic gene pair that was regulated by p53 and NF-Y in lung cancer. However, their role and regulatory mechanism in breast cancer remain elusive. In this study, we found that the expression levels of PRR11 and SKA2 were upregulated and have a negative prognotic value in breast cancer. Loss-of-function experiments showed that RNAi-mediated knockdown of PRR11 and/or SKA2 inhibited proliferation, migration, and invasion of breast cancer cells. Mechanistic experiments revealed that knockdown of PRR11 and/or SKA2 caused dysregulation of several downstream genes, including CDK6, TPM3, and USP12, etc. Luciferase reporter assays demonstrated that wild type p53 significantly repressed the PRR11-SKA2 bidirectional promoter activity, but not NF-Y. Interestingly, NF-Y was only essential for and correlated with the expression of PRR11, but not SKA2. Consistently, adriamycin-induced (ADR) activation of endogenous p53 also caused significant repression of the PRR11 and SKA2 gene pair expression. Notably, breast cancer patients with lower expression levels of either PRR11 or SKA2, along with wild type p53, exhibited better disease-free survival compared to others with p53 mutations and/or higher expression levels of either PRR11 or SKA2. Collectively, our study indicates that the PRR11 and SKA2 transcription unit might be an oncogenic contributor and might serve as a novel diagnostic and therapeutic target in breast cancer.
Keywords: Breast cancer, p53, PRR11, SKA2


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