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LncRNA DLEU1 contributes to colorectal cancer progression via activation of KPNA3

BACKGROUND: Accumulating evidences show that long noncoding RNAs (lncRNA) play essential roles in the development and progression of various malignancies. However, their functions remains poorly understood and many lncRNAs have not been defined in colorectal cancer (CRC). In this study, we investiga...

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Autores principales: Liu, Tianyou, Han, Zhiyang, Li, Huanyu, Zhu, Yuekun, Sun, Ziquan, Zhu, Anlong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087004/
https://www.ncbi.nlm.nih.gov/pubmed/30098595
http://dx.doi.org/10.1186/s12943-018-0873-2
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author Liu, Tianyou
Han, Zhiyang
Li, Huanyu
Zhu, Yuekun
Sun, Ziquan
Zhu, Anlong
author_facet Liu, Tianyou
Han, Zhiyang
Li, Huanyu
Zhu, Yuekun
Sun, Ziquan
Zhu, Anlong
author_sort Liu, Tianyou
collection PubMed
description BACKGROUND: Accumulating evidences show that long noncoding RNAs (lncRNA) play essential roles in the development and progression of various malignancies. However, their functions remains poorly understood and many lncRNAs have not been defined in colorectal cancer (CRC). In this study, we investigated the role of DLEU1 in CRC. METHODS: Quantitative real-time PCR was used to detect the expression of DLEU1 and survival analysis was adopted to explore the association between DLEU1 expression and the prognosis of CRC patients. CRC cells were stably transfected with lentivirus approach and cell proliferation, migration, invasion and cell apoptosis, as well as tumorigenesis in nude mice were performed to assess the effects of DLEU1 in BCa. Biotin-coupled probe pull down assay, RNA immunoprecipitation and Fluorescence in situ hybridization assays were conducted to confirm the relationship between DLEU1 and SMARCA1. RESULTS: Here we revealed that DLEU1 was crucial for activation of KPNA3 by recruiting SMARCA1, an essential subunit of the NURF chromatin remodeling complex, in CRC. DLEU1 was indispensible for the deposition of SMARCA1 at the promoter of KPNA3 gene. Increased expression of DLEU1 and KPNA3 was observed in human CRC tissues. And higher expression of DLEU1 or KPNA3 in patients indicates lower survival rate and poorer prognosis. DLEU1 knockdown remarkably inhibited CRC cell proliferation, migration and invasion in vitro and in vivo while overexpressing KPNA3 in the meantime reversed it. CONCLUSIONS: Our results identify DLEU1 as a key regulator by a novel DLEU1/SMARCA1/KPNA3 axis in CRC development and progression, which may provide a potential biomarker and therapeutic target for the management of CRC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12943-018-0873-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-60870042018-08-20 LncRNA DLEU1 contributes to colorectal cancer progression via activation of KPNA3 Liu, Tianyou Han, Zhiyang Li, Huanyu Zhu, Yuekun Sun, Ziquan Zhu, Anlong Mol Cancer Research BACKGROUND: Accumulating evidences show that long noncoding RNAs (lncRNA) play essential roles in the development and progression of various malignancies. However, their functions remains poorly understood and many lncRNAs have not been defined in colorectal cancer (CRC). In this study, we investigated the role of DLEU1 in CRC. METHODS: Quantitative real-time PCR was used to detect the expression of DLEU1 and survival analysis was adopted to explore the association between DLEU1 expression and the prognosis of CRC patients. CRC cells were stably transfected with lentivirus approach and cell proliferation, migration, invasion and cell apoptosis, as well as tumorigenesis in nude mice were performed to assess the effects of DLEU1 in BCa. Biotin-coupled probe pull down assay, RNA immunoprecipitation and Fluorescence in situ hybridization assays were conducted to confirm the relationship between DLEU1 and SMARCA1. RESULTS: Here we revealed that DLEU1 was crucial for activation of KPNA3 by recruiting SMARCA1, an essential subunit of the NURF chromatin remodeling complex, in CRC. DLEU1 was indispensible for the deposition of SMARCA1 at the promoter of KPNA3 gene. Increased expression of DLEU1 and KPNA3 was observed in human CRC tissues. And higher expression of DLEU1 or KPNA3 in patients indicates lower survival rate and poorer prognosis. DLEU1 knockdown remarkably inhibited CRC cell proliferation, migration and invasion in vitro and in vivo while overexpressing KPNA3 in the meantime reversed it. CONCLUSIONS: Our results identify DLEU1 as a key regulator by a novel DLEU1/SMARCA1/KPNA3 axis in CRC development and progression, which may provide a potential biomarker and therapeutic target for the management of CRC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12943-018-0873-2) contains supplementary material, which is available to authorized users. BioMed Central 2018-08-11 /pmc/articles/PMC6087004/ /pubmed/30098595 http://dx.doi.org/10.1186/s12943-018-0873-2 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Liu, Tianyou
Han, Zhiyang
Li, Huanyu
Zhu, Yuekun
Sun, Ziquan
Zhu, Anlong
LncRNA DLEU1 contributes to colorectal cancer progression via activation of KPNA3
title LncRNA DLEU1 contributes to colorectal cancer progression via activation of KPNA3
title_full LncRNA DLEU1 contributes to colorectal cancer progression via activation of KPNA3
title_fullStr LncRNA DLEU1 contributes to colorectal cancer progression via activation of KPNA3
title_full_unstemmed LncRNA DLEU1 contributes to colorectal cancer progression via activation of KPNA3
title_short LncRNA DLEU1 contributes to colorectal cancer progression via activation of KPNA3
title_sort lncrna dleu1 contributes to colorectal cancer progression via activation of kpna3
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087004/
https://www.ncbi.nlm.nih.gov/pubmed/30098595
http://dx.doi.org/10.1186/s12943-018-0873-2
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