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

// Qingjian Wu 1, * , Fan Yang 2, * , Zhenxing Yang 1 , Zhenqiang Fang 1 , Wanlei Fu 3 , Wei Chen 1 , Xiaobing Liu 1 , Jiang Zhao 1 , Qingqing Wang 1 , Xiaoyan Hu 1 and Longkun Li 1 1 Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China 2 Center of Medical Experiment & Technique, Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China 3 Department 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.