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A Novel Long Non-Coding RNA-01488 Suppressed Metastasis and Tumorigenesis by Inducing miRNAs That Reduce Vimentin Expression and Ubiquitination of Cyclin E

Long intergenic non-coding RNAs (lincRNAs) play important roles in human cancer development, including cell differentiation, apoptosis, and tumor progression. However, their underlying mechanisms of action are largely unknown at present. In this study, we focused on a novel suppressor lincRNA that h...

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Autores principales: Lin, Syuan-Ling, Lin, Yang-Hsiang, Chi, Hsiang-Cheng, Lin, Tzu-Kang, Chen, Wei-Jan, Yeh, Chau-Ting, Lin, Kwang-Huei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348830/
https://www.ncbi.nlm.nih.gov/pubmed/32575745
http://dx.doi.org/10.3390/cells9061504
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author Lin, Syuan-Ling
Lin, Yang-Hsiang
Chi, Hsiang-Cheng
Lin, Tzu-Kang
Chen, Wei-Jan
Yeh, Chau-Ting
Lin, Kwang-Huei
author_facet Lin, Syuan-Ling
Lin, Yang-Hsiang
Chi, Hsiang-Cheng
Lin, Tzu-Kang
Chen, Wei-Jan
Yeh, Chau-Ting
Lin, Kwang-Huei
author_sort Lin, Syuan-Ling
collection PubMed
description Long intergenic non-coding RNAs (lincRNAs) play important roles in human cancer development, including cell differentiation, apoptosis, and tumor progression. However, their underlying mechanisms of action are largely unknown at present. In this study, we focused on a novel suppressor lincRNA that has the potential to inhibit progression of human hepatocellular carcinoma (HCC). Our experiments disclosed long intergenic non-protein coding RNA 1488 (LINC01488) as a key negative regulator of HCC. Clinically, patients with high LINC01488 expression displayed greater survival rates and better prognosis. In vitro and in vivo functional assays showed that LINC01488 overexpression leads to significant suppression of cell proliferation and metastasis in HCC. Furthermore, LINC01488 bound to cyclin E to induce its ubiquitination and reduced expression of vimentin mediated by both miR-124-3p/miR-138-5p. Our results collectively indicate that LINC01488 acts as a tumor suppressor that inhibits metastasis and tumorigenesis in HCC via the miR-124-3p/miR-138-5p/vimentin axis. Furthermore, LINC01488 interacts with and degrades cyclin E, which contributes to its anti-tumorigenic activity. In view of these findings, we propose that enhancement of LINC01488 expression could be effective as a potential therapeutic strategy for HCC.
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spelling pubmed-73488302020-07-22 A Novel Long Non-Coding RNA-01488 Suppressed Metastasis and Tumorigenesis by Inducing miRNAs That Reduce Vimentin Expression and Ubiquitination of Cyclin E Lin, Syuan-Ling Lin, Yang-Hsiang Chi, Hsiang-Cheng Lin, Tzu-Kang Chen, Wei-Jan Yeh, Chau-Ting Lin, Kwang-Huei Cells Article Long intergenic non-coding RNAs (lincRNAs) play important roles in human cancer development, including cell differentiation, apoptosis, and tumor progression. However, their underlying mechanisms of action are largely unknown at present. In this study, we focused on a novel suppressor lincRNA that has the potential to inhibit progression of human hepatocellular carcinoma (HCC). Our experiments disclosed long intergenic non-protein coding RNA 1488 (LINC01488) as a key negative regulator of HCC. Clinically, patients with high LINC01488 expression displayed greater survival rates and better prognosis. In vitro and in vivo functional assays showed that LINC01488 overexpression leads to significant suppression of cell proliferation and metastasis in HCC. Furthermore, LINC01488 bound to cyclin E to induce its ubiquitination and reduced expression of vimentin mediated by both miR-124-3p/miR-138-5p. Our results collectively indicate that LINC01488 acts as a tumor suppressor that inhibits metastasis and tumorigenesis in HCC via the miR-124-3p/miR-138-5p/vimentin axis. Furthermore, LINC01488 interacts with and degrades cyclin E, which contributes to its anti-tumorigenic activity. In view of these findings, we propose that enhancement of LINC01488 expression could be effective as a potential therapeutic strategy for HCC. MDPI 2020-06-20 /pmc/articles/PMC7348830/ /pubmed/32575745 http://dx.doi.org/10.3390/cells9061504 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lin, Syuan-Ling
Lin, Yang-Hsiang
Chi, Hsiang-Cheng
Lin, Tzu-Kang
Chen, Wei-Jan
Yeh, Chau-Ting
Lin, Kwang-Huei
A Novel Long Non-Coding RNA-01488 Suppressed Metastasis and Tumorigenesis by Inducing miRNAs That Reduce Vimentin Expression and Ubiquitination of Cyclin E
title A Novel Long Non-Coding RNA-01488 Suppressed Metastasis and Tumorigenesis by Inducing miRNAs That Reduce Vimentin Expression and Ubiquitination of Cyclin E
title_full A Novel Long Non-Coding RNA-01488 Suppressed Metastasis and Tumorigenesis by Inducing miRNAs That Reduce Vimentin Expression and Ubiquitination of Cyclin E
title_fullStr A Novel Long Non-Coding RNA-01488 Suppressed Metastasis and Tumorigenesis by Inducing miRNAs That Reduce Vimentin Expression and Ubiquitination of Cyclin E
title_full_unstemmed A Novel Long Non-Coding RNA-01488 Suppressed Metastasis and Tumorigenesis by Inducing miRNAs That Reduce Vimentin Expression and Ubiquitination of Cyclin E
title_short A Novel Long Non-Coding RNA-01488 Suppressed Metastasis and Tumorigenesis by Inducing miRNAs That Reduce Vimentin Expression and Ubiquitination of Cyclin E
title_sort novel long non-coding rna-01488 suppressed metastasis and tumorigenesis by inducing mirnas that reduce vimentin expression and ubiquitination of cyclin e
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348830/
https://www.ncbi.nlm.nih.gov/pubmed/32575745
http://dx.doi.org/10.3390/cells9061504
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