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MicroRNA-338 Inhibits Growth, Invasion and Metastasis of Gastric Cancer by Targeting NRP1 Expression

NRP1 as multifunctional non-tyrosine-kinase receptors play critical roles in tumor progression. MicroRNAs (miRNAs) are an important class of pervasive genes that are involved in a variety of biological functions, particularly cancer. It remains unclear whether miRNAs can regulate the expression of N...

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Autores principales: Peng, Yang, Liu, Yan-Min, Li, Lu-Chun, Wang, Lu-Lu, Wu, Xiao-Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988047/
https://www.ncbi.nlm.nih.gov/pubmed/24736504
http://dx.doi.org/10.1371/journal.pone.0094422
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author Peng, Yang
Liu, Yan-Min
Li, Lu-Chun
Wang, Lu-Lu
Wu, Xiao-Ling
author_facet Peng, Yang
Liu, Yan-Min
Li, Lu-Chun
Wang, Lu-Lu
Wu, Xiao-Ling
author_sort Peng, Yang
collection PubMed
description NRP1 as multifunctional non-tyrosine-kinase receptors play critical roles in tumor progression. MicroRNAs (miRNAs) are an important class of pervasive genes that are involved in a variety of biological functions, particularly cancer. It remains unclear whether miRNAs can regulate the expression of NRP1. The goal of this study was to identify miRNAs that could inhibit the growth, invasion and metastasis of gastric cancer by targeting NRP1 expression. We found that miR-338 expression was reduced in gastric cancer cell lines and in gastric cancer tissues. Moreover, we found that miR-338 inhibited gastric cancer cell migration, invasion, proliferation and promoted apoptosis by targeting NRP1 expression. As an upstream regulator of NRP1, miR-338 directly targets NRP1. The forced expression of miR-338 inhibited the phosphorylation of Erk1/2, P38 MAPK and Akt; however, the expression of phosphorylated Erk1/2, P38 MAPK and Akt was restored by the overexpression of NRP1. In AGS cells infected with miR-338 or transfected with SiNRP1, the protein levels of fibronectin, vimentin, N-cadherin and SNAIL were decreased, but the expression of E-cadherin was increased. The expression of mesenchymal markers in miR-338-expressing cells was restored to normal levels by the restoration of NRP1 expression. In vivo, miR-338 also decreased tumor growth and suppressed D-MVA by targeting NRP1. Therefore, we conclude that miR-338 acts as a novel tumor suppressor gene in gastric cancer. miR-338 can decrease migratory, invasive, proliferative and apoptotic behaviors, as well as gastric cancer EMT, by attenuating the expression of NRP1.
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spelling pubmed-39880472014-04-21 MicroRNA-338 Inhibits Growth, Invasion and Metastasis of Gastric Cancer by Targeting NRP1 Expression Peng, Yang Liu, Yan-Min Li, Lu-Chun Wang, Lu-Lu Wu, Xiao-Ling PLoS One Research Article NRP1 as multifunctional non-tyrosine-kinase receptors play critical roles in tumor progression. MicroRNAs (miRNAs) are an important class of pervasive genes that are involved in a variety of biological functions, particularly cancer. It remains unclear whether miRNAs can regulate the expression of NRP1. The goal of this study was to identify miRNAs that could inhibit the growth, invasion and metastasis of gastric cancer by targeting NRP1 expression. We found that miR-338 expression was reduced in gastric cancer cell lines and in gastric cancer tissues. Moreover, we found that miR-338 inhibited gastric cancer cell migration, invasion, proliferation and promoted apoptosis by targeting NRP1 expression. As an upstream regulator of NRP1, miR-338 directly targets NRP1. The forced expression of miR-338 inhibited the phosphorylation of Erk1/2, P38 MAPK and Akt; however, the expression of phosphorylated Erk1/2, P38 MAPK and Akt was restored by the overexpression of NRP1. In AGS cells infected with miR-338 or transfected with SiNRP1, the protein levels of fibronectin, vimentin, N-cadherin and SNAIL were decreased, but the expression of E-cadherin was increased. The expression of mesenchymal markers in miR-338-expressing cells was restored to normal levels by the restoration of NRP1 expression. In vivo, miR-338 also decreased tumor growth and suppressed D-MVA by targeting NRP1. Therefore, we conclude that miR-338 acts as a novel tumor suppressor gene in gastric cancer. miR-338 can decrease migratory, invasive, proliferative and apoptotic behaviors, as well as gastric cancer EMT, by attenuating the expression of NRP1. Public Library of Science 2014-04-15 /pmc/articles/PMC3988047/ /pubmed/24736504 http://dx.doi.org/10.1371/journal.pone.0094422 Text en © 2014 Peng, et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Peng, Yang
Liu, Yan-Min
Li, Lu-Chun
Wang, Lu-Lu
Wu, Xiao-Ling
MicroRNA-338 Inhibits Growth, Invasion and Metastasis of Gastric Cancer by Targeting NRP1 Expression
title MicroRNA-338 Inhibits Growth, Invasion and Metastasis of Gastric Cancer by Targeting NRP1 Expression
title_full MicroRNA-338 Inhibits Growth, Invasion and Metastasis of Gastric Cancer by Targeting NRP1 Expression
title_fullStr MicroRNA-338 Inhibits Growth, Invasion and Metastasis of Gastric Cancer by Targeting NRP1 Expression
title_full_unstemmed MicroRNA-338 Inhibits Growth, Invasion and Metastasis of Gastric Cancer by Targeting NRP1 Expression
title_short MicroRNA-338 Inhibits Growth, Invasion and Metastasis of Gastric Cancer by Targeting NRP1 Expression
title_sort microrna-338 inhibits growth, invasion and metastasis of gastric cancer by targeting nrp1 expression
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988047/
https://www.ncbi.nlm.nih.gov/pubmed/24736504
http://dx.doi.org/10.1371/journal.pone.0094422
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