LncRNA DLEU1 contributes to colorectal cancer progression via activation of KPNA3
Abstract 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 i...
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BMC
2018-08-01
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Series: | Molecular Cancer |
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Online Access: | http://link.springer.com/article/10.1186/s12943-018-0873-2 |
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author | Tianyou Liu Zhiyang Han Huanyu Li Yuekun Zhu Ziquan Sun Anlong Zhu |
author_facet | Tianyou Liu Zhiyang Han Huanyu Li Yuekun Zhu Ziquan Sun Anlong Zhu |
author_sort | Tianyou Liu |
collection | DOAJ |
description | Abstract 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. |
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institution | Directory Open Access Journal |
issn | 1476-4598 |
language | English |
last_indexed | 2024-12-15T00:19:26Z |
publishDate | 2018-08-01 |
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series | Molecular Cancer |
spelling | doaj.art-60130be1109949acaa8214a113f6fcee2022-12-21T22:42:21ZengBMCMolecular Cancer1476-45982018-08-0117111310.1186/s12943-018-0873-2LncRNA DLEU1 contributes to colorectal cancer progression via activation of KPNA3Tianyou Liu0Zhiyang Han1Huanyu Li2Yuekun Zhu3Ziquan Sun4Anlong Zhu5Department of General Surgery, The First Affiliated Hospital of Harbin Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Harbin Medical UniversityDepartment of General Surgery, Mulan Country People’s HospitalDepartment of General Surgery, The First Affiliated Hospital of Harbin Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Harbin Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Harbin Medical UniversityAbstract 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.http://link.springer.com/article/10.1186/s12943-018-0873-2DLEU1Colorectal cancerProgressionSMARCA1KPNA3 |
spellingShingle | Tianyou Liu Zhiyang Han Huanyu Li Yuekun Zhu Ziquan Sun Anlong Zhu LncRNA DLEU1 contributes to colorectal cancer progression via activation of KPNA3 Molecular Cancer DLEU1 Colorectal cancer Progression SMARCA1 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 | DLEU1 Colorectal cancer Progression SMARCA1 KPNA3 |
url | http://link.springer.com/article/10.1186/s12943-018-0873-2 |
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