Journal
ONCOTARGET
Volume 8, Issue 49, Pages 85353-85367Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.19743
Keywords
PVT1; ccRCC; ceRNA; alternative splicing; miR-200s
Categories
Funding
- National Natural Science Foundation of China [31372562, 81470935, 81402105, 81670645, 81602236]
- National Major Scientific and Technological Special Project for Significant New Drugs Development [2012ZX09303018]
- Chenguang Program of Wuhan Science and Technology Bureau [2015070404010199]
- National High Technology Research and Development Program 863 [2014AA020607]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available