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Antisense lncRNA LDLRAD4-AS1 promotes metastasis by decreasing the expression of LDLRAD4 and predicts a poor prognosis in colorectal cancer

Long noncoding RNAs (lncRNAs) have been revealed to play critical roles in tumor initiation and progression. The antisense lncRNA LDLRAD4-AS1 is the longest lncRNA of LDLRAD4, and its expression levels, cellular localization, precise function, and mechanism in colorectal cancer (CRC) remain unknown....

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Autores principales: Mo, Shaobo, Zhang, Long, Dai, Weixing, Han, Lingyu, Wang, Renjie, Xiang, Wenqiang, Wang, Zhimin, Li, Qingguo, Yu, Jun, Yuan, Jihang, Cai, Sanjun, Cai, Guoxiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048743/
https://www.ncbi.nlm.nih.gov/pubmed/32111819
http://dx.doi.org/10.1038/s41419-020-2338-y
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author Mo, Shaobo
Zhang, Long
Dai, Weixing
Han, Lingyu
Wang, Renjie
Xiang, Wenqiang
Wang, Zhimin
Li, Qingguo
Yu, Jun
Yuan, Jihang
Cai, Sanjun
Cai, Guoxiang
author_facet Mo, Shaobo
Zhang, Long
Dai, Weixing
Han, Lingyu
Wang, Renjie
Xiang, Wenqiang
Wang, Zhimin
Li, Qingguo
Yu, Jun
Yuan, Jihang
Cai, Sanjun
Cai, Guoxiang
author_sort Mo, Shaobo
collection PubMed
description Long noncoding RNAs (lncRNAs) have been revealed to play critical roles in tumor initiation and progression. The antisense lncRNA LDLRAD4-AS1 is the longest lncRNA of LDLRAD4, and its expression levels, cellular localization, precise function, and mechanism in colorectal cancer (CRC) remain unknown. In this study, we observed that lncRNA LDLRAD4-AS1 was located in the nucleus of CRC cells and that lncRNA LDLRAD4-AS1 was upregulated in most CRC specimens and cell lines. Overexpression of lncRNA LDLRAD4-AS1 was correlated with poor prognosis in CRC patients. LncRNA LDLRAD4-AS1 upregulation enhanced the migration and invasion of CRC cells in vitro and facilitated CRC metastasis in vivo. Mechanistic investigations suggested that lncRNA LDLRAD4-AS1 could decrease the expression of LDLRAD4 by disrupting the stability of LDLRAD4 mRNA, resulting in epithelial-to-mesenchymal transition (EMT) through upregulating Snail, thereby promoting metastasis in CRC. Our results demonstrated a previously unrecognized LDLRAD4-AS1-LDLRAD4-Snail regulatory axis involved in epigenetic and posttranscriptional regulation that contributes to CRC progression and metastasis.
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spelling pubmed-70487432020-03-04 Antisense lncRNA LDLRAD4-AS1 promotes metastasis by decreasing the expression of LDLRAD4 and predicts a poor prognosis in colorectal cancer Mo, Shaobo Zhang, Long Dai, Weixing Han, Lingyu Wang, Renjie Xiang, Wenqiang Wang, Zhimin Li, Qingguo Yu, Jun Yuan, Jihang Cai, Sanjun Cai, Guoxiang Cell Death Dis Article Long noncoding RNAs (lncRNAs) have been revealed to play critical roles in tumor initiation and progression. The antisense lncRNA LDLRAD4-AS1 is the longest lncRNA of LDLRAD4, and its expression levels, cellular localization, precise function, and mechanism in colorectal cancer (CRC) remain unknown. In this study, we observed that lncRNA LDLRAD4-AS1 was located in the nucleus of CRC cells and that lncRNA LDLRAD4-AS1 was upregulated in most CRC specimens and cell lines. Overexpression of lncRNA LDLRAD4-AS1 was correlated with poor prognosis in CRC patients. LncRNA LDLRAD4-AS1 upregulation enhanced the migration and invasion of CRC cells in vitro and facilitated CRC metastasis in vivo. Mechanistic investigations suggested that lncRNA LDLRAD4-AS1 could decrease the expression of LDLRAD4 by disrupting the stability of LDLRAD4 mRNA, resulting in epithelial-to-mesenchymal transition (EMT) through upregulating Snail, thereby promoting metastasis in CRC. Our results demonstrated a previously unrecognized LDLRAD4-AS1-LDLRAD4-Snail regulatory axis involved in epigenetic and posttranscriptional regulation that contributes to CRC progression and metastasis. Nature Publishing Group UK 2020-02-28 /pmc/articles/PMC7048743/ /pubmed/32111819 http://dx.doi.org/10.1038/s41419-020-2338-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Mo, Shaobo
Zhang, Long
Dai, Weixing
Han, Lingyu
Wang, Renjie
Xiang, Wenqiang
Wang, Zhimin
Li, Qingguo
Yu, Jun
Yuan, Jihang
Cai, Sanjun
Cai, Guoxiang
Antisense lncRNA LDLRAD4-AS1 promotes metastasis by decreasing the expression of LDLRAD4 and predicts a poor prognosis in colorectal cancer
title Antisense lncRNA LDLRAD4-AS1 promotes metastasis by decreasing the expression of LDLRAD4 and predicts a poor prognosis in colorectal cancer
title_full Antisense lncRNA LDLRAD4-AS1 promotes metastasis by decreasing the expression of LDLRAD4 and predicts a poor prognosis in colorectal cancer
title_fullStr Antisense lncRNA LDLRAD4-AS1 promotes metastasis by decreasing the expression of LDLRAD4 and predicts a poor prognosis in colorectal cancer
title_full_unstemmed Antisense lncRNA LDLRAD4-AS1 promotes metastasis by decreasing the expression of LDLRAD4 and predicts a poor prognosis in colorectal cancer
title_short Antisense lncRNA LDLRAD4-AS1 promotes metastasis by decreasing the expression of LDLRAD4 and predicts a poor prognosis in colorectal cancer
title_sort antisense lncrna ldlrad4-as1 promotes metastasis by decreasing the expression of ldlrad4 and predicts a poor prognosis in colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048743/
https://www.ncbi.nlm.nih.gov/pubmed/32111819
http://dx.doi.org/10.1038/s41419-020-2338-y
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