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Oncotarget. 2017 Jul 31;8(49):85353-85367. doi: 10.18632/oncotarget.19743. eCollection 2017 Oct 17.

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

Yang T1,2,3, Zhou H1,2, Liu P1,2, Yan L1,2, Yao W1,2, Chen K1,2, Zeng J1,2, Li H1,2, Hu J1,2, Xu H1,2, Ye Z1,2.

Author information

1
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
2
Hubei Institute of Urology, Wuhan 430030, PR China.
3
Department of Urology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou 434020, PR China.

Abstract

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.

KEYWORDS:

PVT1; alternative splicing; ccRCC; ceRNA; miR-200s

Conflict of interest statement

CONFLICTS OF INTEREST The authors declared no conflicts of interest.

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