Oncotarget

Research Papers:

PinX1 serves as a potential prognostic indicator for clear cell renal cell carcinoma and inhibits its invasion and metastasis by suppressing MMP-2 via NF-κB-dependent transcription

Hai-Long Li _, Li Han, Hai-Rong Chen, Fei Meng, Qing-Hua Liu, Zhen-Qiang Pan, Jin Bai and Jun-Nian Zheng

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Oncotarget. 2015; 6:21406-21420. https://doi.org/10.18632/oncotarget.4011

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Abstract

Hai-Long Li1,2,3,*, Li Han2,*, Hai-Rong Chen6,*, Fei Meng2, Qing-Hua Liu2, Zhen-Qiang Pan2,5, Jin Bai2,5, Jun-Nian Zheng1,2,3,4

1The First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, China

2Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, Jiangsu, China

3Department of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China

4Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China

5Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA

6Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China

*These authors have contributed equally to this work

Correspondence to:

Jin Bai, e-mail: bj@xzmc.edu.cn

Jun-Nian Zheng, e-mail: jnzheng@xzmc.edu.cn

Keywords: pinX1, metastasis, prognostic, MMP-2, NF-κB

Received: January 15, 2015     Accepted: May 14, 2015     Published: May 27, 2015

ABSTRACT

PIN2/TRF1-interacting telomerase inhibitor 1 (PinX1) is a novel cloned gene which has been identified as a major haploinsufficient tumor suppressor essential for maintaining telomerase activity, the length of telomerase and chromosome stability. This study explored the clinical significance and biological function of PinX1 in human clear cell renal cell carcinoma (ccRCC). The clinical relevance of PinX1 in ccRCC was evaluated using tissue microarray and immunohistochemical staining in two independent human ccRCC cohorts. Our data demonstrated that PinX1 expression was dramatically decreased in ccRCC tissues compared with normal renal tissues and paired adjacent non-tumor tissues. Low PinX1 expression was significantly correlated with depth of invasion, lymph node metastasis and advanced TNM stage in patients, as well as with worse overall and disease-specific survival. Cox regression analysis revealed that PinX1 expression was an independent prognostic factor for ccRCC patients. Moreover, PinX1 inhibited the migration and invasion of ccRCC by suppressing MMP-2 expression and activity via NF-κB-dependent transcription in vitro. In vivo studies confirmed that PinX1 negatively regulated ccRCC metastasis and the expression of MMP-2 and NF-κB-p65. These findings indicate that PinX1 suppresses ccRCC metastasis and may serve as a ccRCC candidate clinical prognostic marker and a potential therapeutic target.


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