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miR-21 and KLF4 jointly augment epithelial-mesenchymal transition via the Akt/ERK1/2 pathway
miR-21 induces epithelial-mesenchymal transition (EMT) of human cholangiocarcinoma (CCA) cells. However, the mechanism by which this occurs remains unclear. In the present study, high throughput platform was employed to detect the genes that are differential expressed in QBC939 cells transfected wit...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363879/ https://www.ncbi.nlm.nih.gov/pubmed/28197636 http://dx.doi.org/10.3892/ijo.2017.3876 |
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author | Liu, Chen-Hai Huang, Qiang Jin, Zhi-Yuan Zhu, Cheng-Lin Liu, Zhen Wang, Chao |
author_facet | Liu, Chen-Hai Huang, Qiang Jin, Zhi-Yuan Zhu, Cheng-Lin Liu, Zhen Wang, Chao |
author_sort | Liu, Chen-Hai |
collection | PubMed |
description | miR-21 induces epithelial-mesenchymal transition (EMT) of human cholangiocarcinoma (CCA) cells. However, the mechanism by which this occurs remains unclear. In the present study, high throughput platform was employed to detect the genes that are differential expressed in QBC939 cells transfected with a hsa-miR-21 antagomir or control vectors. The EMT-related Krüppel-like factor 4 (KLF4) gene was down-regulated after miR-21 was knocked down. Overexpression of miR-21 upregulated KLF4, Akt, ERK and mesenchymal cell markers (N-cadherin and vimentin), downregulated the expression of epithelial cell marker E-cadherin and reduced cell migration and invasion. Immunohistochemistry showed that KLF4, pAkt and pERK were upregulated in tumor xenografts transfected with miR-21 mimics. Inhibitors of the PI3K-Akt and ERK1/2 pathways, LY294002 and U0126, significantly suppressed the EMT phenotype. The present data demonstrated that overexpression of miR-21, accompanied with KLF4, augmented the EMT via inactivation of Akt and ERK1/2 pathways. In conclusion, we have identified a novel mechanism that may be targeted in an attempt to relieve the malignant biological behavior of CCA cells. |
format | Online Article Text |
id | pubmed-5363879 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-53638792017-04-12 miR-21 and KLF4 jointly augment epithelial-mesenchymal transition via the Akt/ERK1/2 pathway Liu, Chen-Hai Huang, Qiang Jin, Zhi-Yuan Zhu, Cheng-Lin Liu, Zhen Wang, Chao Int J Oncol Articles miR-21 induces epithelial-mesenchymal transition (EMT) of human cholangiocarcinoma (CCA) cells. However, the mechanism by which this occurs remains unclear. In the present study, high throughput platform was employed to detect the genes that are differential expressed in QBC939 cells transfected with a hsa-miR-21 antagomir or control vectors. The EMT-related Krüppel-like factor 4 (KLF4) gene was down-regulated after miR-21 was knocked down. Overexpression of miR-21 upregulated KLF4, Akt, ERK and mesenchymal cell markers (N-cadherin and vimentin), downregulated the expression of epithelial cell marker E-cadherin and reduced cell migration and invasion. Immunohistochemistry showed that KLF4, pAkt and pERK were upregulated in tumor xenografts transfected with miR-21 mimics. Inhibitors of the PI3K-Akt and ERK1/2 pathways, LY294002 and U0126, significantly suppressed the EMT phenotype. The present data demonstrated that overexpression of miR-21, accompanied with KLF4, augmented the EMT via inactivation of Akt and ERK1/2 pathways. In conclusion, we have identified a novel mechanism that may be targeted in an attempt to relieve the malignant biological behavior of CCA cells. D.A. Spandidos 2017-02-14 /pmc/articles/PMC5363879/ /pubmed/28197636 http://dx.doi.org/10.3892/ijo.2017.3876 Text en Copyright: © Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Liu, Chen-Hai Huang, Qiang Jin, Zhi-Yuan Zhu, Cheng-Lin Liu, Zhen Wang, Chao miR-21 and KLF4 jointly augment epithelial-mesenchymal transition via the Akt/ERK1/2 pathway |
title | miR-21 and KLF4 jointly augment epithelial-mesenchymal transition via the Akt/ERK1/2 pathway |
title_full | miR-21 and KLF4 jointly augment epithelial-mesenchymal transition via the Akt/ERK1/2 pathway |
title_fullStr | miR-21 and KLF4 jointly augment epithelial-mesenchymal transition via the Akt/ERK1/2 pathway |
title_full_unstemmed | miR-21 and KLF4 jointly augment epithelial-mesenchymal transition via the Akt/ERK1/2 pathway |
title_short | miR-21 and KLF4 jointly augment epithelial-mesenchymal transition via the Akt/ERK1/2 pathway |
title_sort | mir-21 and klf4 jointly augment epithelial-mesenchymal transition via the akt/erk1/2 pathway |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363879/ https://www.ncbi.nlm.nih.gov/pubmed/28197636 http://dx.doi.org/10.3892/ijo.2017.3876 |
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