Research Papers:

lncRNA PVT1 and its splicing variant function as competing endogenous RNA to regulate clear cell renal cell carcinoma progression

Tao Yang, Hui Zhou, Peijun Liu, Libin Yan, Weimin Yao, Ke Chen, Jin Zeng, Heng Li, Junhui Hu, Hua Xu _ and Zhangqun Ye

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Oncotarget. 2017; 8:85353-85367. https://doi.org/10.18632/oncotarget.19743

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Tao Yang1,2,3,*, Hui Zhou1,2,*, Peijun Liu1,2, Libin Yan1,2, Weimin Yao1,2, Ke Chen1,2, Jin Zeng1,2, Heng Li1,2, Junhui Hu1,2, Hua Xu1,2 and Zhangqun Ye1,2

1Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China

2Hubei Institute of Urology, Wuhan 430030, PR China

3Department of Urology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou 434020, PR China

*These authors have contributed equally to this work

Correspondence to:

Hua Xu, email: [email protected]

Keywords: PVT1, ccRCC, ceRNA, alternative splicing, miR-200s

Abbreviations: PVT1: Plasmacytoma variant translocation 1, ccRCC: clear cell renal cell carcinoma, RIP: RNA immunoprecipitation, OS: overall survival, DFS: disease free survival

Received: February 28, 2017     Accepted: June 19, 2017     Published: July 31, 2017


Long non-coding RNAs (lncRNAs) exert critical regulatory roles in the development and progression of several cancers. Plasmacytoma variant translocation 1 (PVT1), an lncRNA, was shown to be upregulated in clear cell renal cell carcinoma (ccRCC) in our study, while Kaplan-Meier curve and Cox regression analysis showed that high expression of PVT1 was associated with poor overall survival (OS) and disease free survival (DFS) in ccRCC patients. In vitro experiments revealed that PVT1 promoted renal cancer cell proliferation, migration, and invasion, while in vivo studies confirmed its oncogenic roles in ccRCC. Further bioinformatic analysis and RNA immunoprecipitation revealed that PVT1 could function as an oncogenic transcript partly through sponging miR-200s to regulate BMI1, ZEB1 and ZEB2 expression. Besides, a novel splicing variant of PVT1 lacking exon 4 (PVT1ΔE4) was found to have a higher expression in ccRCC and could also promote cell proliferation and invasion as the full-length transcript did. Besides, SRSF1 decreased the inclusion of exon 4 of full-length transcript and increased the relative expression of PVT1ΔE4 in ccRCC. Mechanistic investigations indicated that PVT1ΔE4 could also upregulate the expression of BMI1, ZEB1 and ZEB2 through interacting with miR-200s. Our study helps reveal new molecular events in ccRCC and provides promising diagnostic and therapeutic targets for this disease.

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