Oncotarget

Research Papers:

OSR1 is a novel epigenetic silenced tumor suppressor regulating invasion and proliferation in renal cell carcinoma

Yixiang Zhang, Yeqing Yuan, Pei Liang, Xiaojing Guo, Ying Ying, Xing-Sheng Shu, Michael Gao Jr and Yingduan Cheng _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:30008-30018. https://doi.org/10.18632/oncotarget.15611

Metrics: PDF 1268 views  |   HTML 1589 views  |   ?  


Abstract

Yixiang Zhang1,*, Yeqing Yuan1,*, Pei Liang2,*, Xiaojing Guo3, Ying Ying4, Xing-Sheng Shu5, Michael Gao Jr2 and Yingduan Cheng6

1Department of Urology, The Second Affiliated Hospital of Jinan University, Shenzhen People’s Hospital, Shenzhen, Guangdong, China

2Department of Urology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California USA

3Department of Pathology, The Second Affiliated Hospital of Jinan University, Shenzhen People’s Hospital, Shenzhen, Guangdong, China

4Department of Physiology, School of Basic Medical Sciences, Shenzhen University Health Sciences Center, Shenzhen, China

5Institute of Molecular Medicine, Health Science Center, Shenzhen University, Shenzhen, China

6Twigbiotechnology, Shenzhen, Guangdong, China

*These authors contribute equally to this work

Correspondence to:

Yingduan Cheng, email: chengyingduan@gmail.com

Keywords: OSR1, methylation, invasion, proliferation, RCC

Received: November 14, 2016    Accepted: January 24, 2017    Published: February 22, 2017

ABSTRACT

Renal cell carcinoma (RCC) is one of the most malignant tumors in human. Here, we found that odd-skipped related transcription factor 1 (OSR1) was downregulated in 769-P and 786-O cells due to promoter CpG methylation. OSR1 expression could be restored by pharmacological demethylation treatment in silenced cell lines. Knockdown of OSR1 in two normal expressed cell lines- A498 and ACHN promoted cell invasion and cellular proliferation. RNA-Sequencing analysis showed that expression profile of genes involved in multiple cancer-related pathways was changed when OSR1 was downregulated. By quantitative real-time PCR, we confirmed that depletion of OSR1 repressed the expression of several tumor suppresor genes involved in p53 pathway, such as p53, p21, p27, p57 and RB in A498 and ACHN. Moreover, knockdown of OSR1 suppressed the transcriptional activity of p53. Of note, OSR1 depletion also led to increased expression of a few oncogenic genes. We further evaluated the clinical significance of OSR1 in primary human RCC specimens by immunohistochemical staining and found that OSR1 expression was downregulated in primary RCC and negatively correlated with histological grade. Thus, our data indicate that OSR1 is a novel tumor suppressor gene in RCC. Downregulation of OSR1 might represent a potentially prognostic marker and therapeutic target for RCC.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 15611