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The PCAT3/PCAT9-miR-203-SNAI2 axis functions as a key mediator for prostate tumor growth and progression
Long non-coding RNAs (lncRNAs) have been reported to be of great importance in the formation and progression of a wide range of human carcinomas including prostate cancer (PCa). Among them, PCAT3 and PCAT9 have been identified as two prostate tissue-specific lncRNAs and are up-regulated in PCa. Howe...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Impact Journals LLC
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844740/ https://www.ncbi.nlm.nih.gov/pubmed/29552304 http://dx.doi.org/10.18632/oncotarget.24198 |
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author | Tao, Fangfang Tian, Xinxin Zhang, Zhiqian |
author_facet | Tao, Fangfang Tian, Xinxin Zhang, Zhiqian |
author_sort | Tao, Fangfang |
collection | PubMed |
description | Long non-coding RNAs (lncRNAs) have been reported to be of great importance in the formation and progression of a wide range of human carcinomas including prostate cancer (PCa). Among them, PCAT3 and PCAT9 have been identified as two prostate tissue-specific lncRNAs and are up-regulated in PCa. However, their roles in the biological characteristics of PCa have not been fully elucidated. In the present study, our data revealed that knockdown of PCAT3 and PCAT9 suppressed cellular proliferation, invasion, migration, angiogenesis and stemness in androgen-dependent LNCaP and 22Rv1 cells. Strikingly, bioinformatics analysis predicted that both PCAT3 and PCAT9 transcripts had two conserved binding sties for miR-203. Meanwhile, dual luciferase report assays revealed that miR-203 could suppress the luciferase activities of reporter plasmids carrying the binding site of miR-203 on the mRNA of PCAT3 or PCAT9. Quantitative RT-PCR (qRT-PCR) and RNA fluorescence in situ hybridization (RNA-FISH) showed that miR-203 mimic reduced the expression of PCAT3 and PCAT9 both in LNCaP and 22Rv1 cells. We also noted that both PCAT3 and PCAT9 inhibited miR-203 expression and alleviated repression on the expression of SNAI2, a critical regulator of epithelial-mesenchymal transition directly targeted by miR-203. Functionally, silence of miR-203 or ectopic expression of SNAI2 attenuated the inhibitory effect of PCAT3 and PCAT9 knockdown on cell proliferation and migration in vitro, and xenograft growth in vivo. Taken together, our data suggested that the PCAT3/PCAT9-miR-203-SNAI2 axis may serve as a promising diagnostic and therapeutic target for PCa. |
format | Online Article Text |
id | pubmed-5844740 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-58447402018-03-16 The PCAT3/PCAT9-miR-203-SNAI2 axis functions as a key mediator for prostate tumor growth and progression Tao, Fangfang Tian, Xinxin Zhang, Zhiqian Oncotarget Research Paper Long non-coding RNAs (lncRNAs) have been reported to be of great importance in the formation and progression of a wide range of human carcinomas including prostate cancer (PCa). Among them, PCAT3 and PCAT9 have been identified as two prostate tissue-specific lncRNAs and are up-regulated in PCa. However, their roles in the biological characteristics of PCa have not been fully elucidated. In the present study, our data revealed that knockdown of PCAT3 and PCAT9 suppressed cellular proliferation, invasion, migration, angiogenesis and stemness in androgen-dependent LNCaP and 22Rv1 cells. Strikingly, bioinformatics analysis predicted that both PCAT3 and PCAT9 transcripts had two conserved binding sties for miR-203. Meanwhile, dual luciferase report assays revealed that miR-203 could suppress the luciferase activities of reporter plasmids carrying the binding site of miR-203 on the mRNA of PCAT3 or PCAT9. Quantitative RT-PCR (qRT-PCR) and RNA fluorescence in situ hybridization (RNA-FISH) showed that miR-203 mimic reduced the expression of PCAT3 and PCAT9 both in LNCaP and 22Rv1 cells. We also noted that both PCAT3 and PCAT9 inhibited miR-203 expression and alleviated repression on the expression of SNAI2, a critical regulator of epithelial-mesenchymal transition directly targeted by miR-203. Functionally, silence of miR-203 or ectopic expression of SNAI2 attenuated the inhibitory effect of PCAT3 and PCAT9 knockdown on cell proliferation and migration in vitro, and xenograft growth in vivo. Taken together, our data suggested that the PCAT3/PCAT9-miR-203-SNAI2 axis may serve as a promising diagnostic and therapeutic target for PCa. Impact Journals LLC 2018-01-12 /pmc/articles/PMC5844740/ /pubmed/29552304 http://dx.doi.org/10.18632/oncotarget.24198 Text en Copyright: © 2018 Tao 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 Tao, Fangfang Tian, Xinxin Zhang, Zhiqian The PCAT3/PCAT9-miR-203-SNAI2 axis functions as a key mediator for prostate tumor growth and progression |
title | The PCAT3/PCAT9-miR-203-SNAI2 axis functions as a key mediator for prostate tumor growth and progression |
title_full | The PCAT3/PCAT9-miR-203-SNAI2 axis functions as a key mediator for prostate tumor growth and progression |
title_fullStr | The PCAT3/PCAT9-miR-203-SNAI2 axis functions as a key mediator for prostate tumor growth and progression |
title_full_unstemmed | The PCAT3/PCAT9-miR-203-SNAI2 axis functions as a key mediator for prostate tumor growth and progression |
title_short | The PCAT3/PCAT9-miR-203-SNAI2 axis functions as a key mediator for prostate tumor growth and progression |
title_sort | pcat3/pcat9-mir-203-snai2 axis functions as a key mediator for prostate tumor growth and progression |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844740/ https://www.ncbi.nlm.nih.gov/pubmed/29552304 http://dx.doi.org/10.18632/oncotarget.24198 |
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