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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |