Cargando…

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

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 regressi...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Tao, Zhou, Hui, Liu, Peijun, Yan, Libin, Yao, Weimin, Chen, Ke, Zeng, Jin, Li, Heng, Hu, Junhui, Xu, Hua, Ye, Zhangqun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689614/
https://www.ncbi.nlm.nih.gov/pubmed/29156724
http://dx.doi.org/10.18632/oncotarget.19743
_version_ 1783279417753075712
author Yang, Tao
Zhou, Hui
Liu, Peijun
Yan, Libin
Yao, Weimin
Chen, Ke
Zeng, Jin
Li, Heng
Hu, Junhui
Xu, Hua
Ye, Zhangqun
author_facet Yang, Tao
Zhou, Hui
Liu, Peijun
Yan, Libin
Yao, Weimin
Chen, Ke
Zeng, Jin
Li, Heng
Hu, Junhui
Xu, Hua
Ye, Zhangqun
author_sort Yang, Tao
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5689614
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-56896142017-11-17 lncRNA PVT1 and its splicing variant function as competing endogenous RNA to regulate clear cell renal cell carcinoma progression Yang, Tao Zhou, Hui Liu, Peijun Yan, Libin Yao, Weimin Chen, Ke Zeng, Jin Li, Heng Hu, Junhui Xu, Hua Ye, Zhangqun Oncotarget Research Paper 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. Impact Journals LLC 2017-07-31 /pmc/articles/PMC5689614/ /pubmed/29156724 http://dx.doi.org/10.18632/oncotarget.19743 Text en Copyright: © 2017 Yang et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Yang, Tao
Zhou, Hui
Liu, Peijun
Yan, Libin
Yao, Weimin
Chen, Ke
Zeng, Jin
Li, Heng
Hu, Junhui
Xu, Hua
Ye, Zhangqun
lncRNA PVT1 and its splicing variant function as competing endogenous RNA to regulate clear cell renal cell carcinoma progression
title lncRNA PVT1 and its splicing variant function as competing endogenous RNA to regulate clear cell renal cell carcinoma progression
title_full lncRNA PVT1 and its splicing variant function as competing endogenous RNA to regulate clear cell renal cell carcinoma progression
title_fullStr lncRNA PVT1 and its splicing variant function as competing endogenous RNA to regulate clear cell renal cell carcinoma progression
title_full_unstemmed lncRNA PVT1 and its splicing variant function as competing endogenous RNA to regulate clear cell renal cell carcinoma progression
title_short lncRNA PVT1 and its splicing variant function as competing endogenous RNA to regulate clear cell renal cell carcinoma progression
title_sort lncrna pvt1 and its splicing variant function as competing endogenous rna to regulate clear cell renal cell carcinoma progression
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689614/
https://www.ncbi.nlm.nih.gov/pubmed/29156724
http://dx.doi.org/10.18632/oncotarget.19743
work_keys_str_mv AT yangtao lncrnapvt1anditssplicingvariantfunctionascompetingendogenousrnatoregulateclearcellrenalcellcarcinomaprogression
AT zhouhui lncrnapvt1anditssplicingvariantfunctionascompetingendogenousrnatoregulateclearcellrenalcellcarcinomaprogression
AT liupeijun lncrnapvt1anditssplicingvariantfunctionascompetingendogenousrnatoregulateclearcellrenalcellcarcinomaprogression
AT yanlibin lncrnapvt1anditssplicingvariantfunctionascompetingendogenousrnatoregulateclearcellrenalcellcarcinomaprogression
AT yaoweimin lncrnapvt1anditssplicingvariantfunctionascompetingendogenousrnatoregulateclearcellrenalcellcarcinomaprogression
AT chenke lncrnapvt1anditssplicingvariantfunctionascompetingendogenousrnatoregulateclearcellrenalcellcarcinomaprogression
AT zengjin lncrnapvt1anditssplicingvariantfunctionascompetingendogenousrnatoregulateclearcellrenalcellcarcinomaprogression
AT liheng lncrnapvt1anditssplicingvariantfunctionascompetingendogenousrnatoregulateclearcellrenalcellcarcinomaprogression
AT hujunhui lncrnapvt1anditssplicingvariantfunctionascompetingendogenousrnatoregulateclearcellrenalcellcarcinomaprogression
AT xuhua lncrnapvt1anditssplicingvariantfunctionascompetingendogenousrnatoregulateclearcellrenalcellcarcinomaprogression
AT yezhangqun lncrnapvt1anditssplicingvariantfunctionascompetingendogenousrnatoregulateclearcellrenalcellcarcinomaprogression