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

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单位: [1]Huazhong Univ Sci & Technol,Tongji Hosp,Dept Urol,Tongji Med Coll,Wuhan 430030,Hubei,Peoples R China [2]Hubei Inst Urol, Wuhan 430030, Hubei, Peoples R China [3]Yangtze Univ, Jingzhou Cent Hosp, Dept Urol, Clin Med Coll 2, Jingzhou 434020, Peoples R China
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关键词: PVT1 ccRCC ceRNA alternative splicing miR-200s

摘要:
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 (PVT1 Delta E4) 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 PVT1 Delta E4 in ccRCC. Mechanistic investigations indicated that PVT1 Delta E4 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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出版当年[2016]版:
大类 | 1 区 医学
小类 | 2 区 细胞生物学 2 区 肿瘤学
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出版当年[2015]版:
Q1 CELL BIOLOGY Q1 ONCOLOGY
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第一作者单位: [1]Huazhong Univ Sci & Technol,Tongji Hosp,Dept Urol,Tongji Med Coll,Wuhan 430030,Hubei,Peoples R China [2]Hubei Inst Urol, Wuhan 430030, Hubei, Peoples R China [3]Yangtze Univ, Jingzhou Cent Hosp, Dept Urol, Clin Med Coll 2, Jingzhou 434020, Peoples R China
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通讯机构: [1]Huazhong Univ Sci & Technol,Tongji Hosp,Dept Urol,Tongji Med Coll,Wuhan 430030,Hubei,Peoples R China [2]Hubei Inst Urol, Wuhan 430030, Hubei, Peoples R China
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