Oncotarget

Research Papers:

Long noncoding RNA PVT1 inhibits renal cancer cell apoptosis by up-regulating Mcl-1

Qingjian Wu, Fan Yang, Zhenxing Yang, Zhenqiang Fang, Wanlei Fu, Wei Chen, Xiaobing Liu, Jiang Zhao, Qingqing Wang, Xiaoyan Hu and Longkun Li _

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Oncotarget. 2017; 8:101865-101875. https://doi.org/10.18632/oncotarget.21706

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Abstract

Qingjian Wu1,*, Fan Yang2,*, Zhenxing Yang1, Zhenqiang Fang1, Wanlei Fu3, Wei Chen1, Xiaobing Liu1, Jiang Zhao1, Qingqing Wang1, Xiaoyan Hu1 and Longkun Li1

1Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China

2Center of Medical Experiment & Technique, Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China

3Department of Pathology, Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China

*These authors have contributed equally to this work

Correspondence to:

Longkun Li, email: lilongk@hotmail.com

Keywords: plasmacytoma variant translocation 1 (PVT1); clear cell renal cell carcinoma (CCRCC); long noncoding RNA (lncRNA); apoptosis

Received: January 12, 2017    Accepted: August 17, 2017    Published: October 09, 2017

ABSTRACT

Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) is up-regulated in various human cancers, and our results indicated that PVT1 was up-regulated in clear cell renal cell carcinoma tissues. The Cancer Genome Atlas cohort analysis revealed that in clear cell renal cell carcinoma, higher PVT1 expression correlated with advanced TNM stage, histological grade, and poor survival. PVT1 knockdown promoted apoptosis, inhibited renal cancer cell proliferation, decreased Mcl-1, and increased cleaved caspase-3 and cleaved PARP. PVT1 increased Mcl-1 mRNA levels in renal cancer cells by promoting mRNA stability without influencing its transcription. in vitro, the enhanced apoptosis arising from PVT1 suppression was attenuated by overexpressing Mcl-1. In addition, in vivo experiments showed that PVT1 knockdown repressed xenograft tumor growth, while Mcl-1 overexpression partially rescued xenograft tumor growth. These results indicate the PVT1/Mcl-1 pathway inhibits renal cancer cell apoptosis in vitro and in vivo. PVT1 may thus serve as a novel biomarker, and the PVT1/Mcl-1 pathway may be a useful therapeutic target for clear cell renal cell carcinoma.


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