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Upregulation of miR-181s reverses mesenchymal transition by targeting KPNA4 in glioblastoma
The goal of this work was to explore the most effective miRNAs affecting glioblastoma multiforme (GBM) phenotype transition and malignant progression. We annotated 491 TCGA samples’ miRNA expression profiles according to their mRNA-based subtypes and found that the mesenchymal tumors had significant...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539550/ https://www.ncbi.nlm.nih.gov/pubmed/26283154 http://dx.doi.org/10.1038/srep13072 |
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author | Wang, Hongjun Tao, Tao Yan, Wei Feng, Yan Wang, Yongzhi Cai, Jinquan You, Yongping Jiang, Tao Jiang, Chuanlu |
author_facet | Wang, Hongjun Tao, Tao Yan, Wei Feng, Yan Wang, Yongzhi Cai, Jinquan You, Yongping Jiang, Tao Jiang, Chuanlu |
author_sort | Wang, Hongjun |
collection | PubMed |
description | The goal of this work was to explore the most effective miRNAs affecting glioblastoma multiforme (GBM) phenotype transition and malignant progression. We annotated 491 TCGA samples’ miRNA expression profiles according to their mRNA-based subtypes and found that the mesenchymal tumors had significantly decreased miR-181 family expression compared with the other three subtypes while the proneural subtype harbored extremely high miR-181 family expression. Patients with high miR-181 family expression had longer overall survival (p = 0.0031). We also confirmed that NF-κB-targeting genes and the EMT (epithelial-mesenchymal transition) pathway were inversely correlated with miR-181 family expression and that the entire miR-181 family inhibited glioma cell invasion and proliferation; of these, miR-181b was the most effective suppressor. Furthermore, miR-181b was validated to suppress EMT by targeting KPNA4 and was associated with survival outcome in the TCGA and CGGA datasets and in another independent cohort. The EMT-inhibitory effect of miR-181b was lost after KPNA4 expression was restored. We also identified the antitumorigenic activity of miR-181b in vitro and in vivo. Our results showed that miR-181 family expression was closely correlated with TCGA subtypes and patients’ overall survival, indicating that miR-181b, a tumor-suppressive miRNA, could be a novel therapeutic candidate for treating gliomas. |
format | Online Article Text |
id | pubmed-4539550 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45395502015-08-26 Upregulation of miR-181s reverses mesenchymal transition by targeting KPNA4 in glioblastoma Wang, Hongjun Tao, Tao Yan, Wei Feng, Yan Wang, Yongzhi Cai, Jinquan You, Yongping Jiang, Tao Jiang, Chuanlu Sci Rep Article The goal of this work was to explore the most effective miRNAs affecting glioblastoma multiforme (GBM) phenotype transition and malignant progression. We annotated 491 TCGA samples’ miRNA expression profiles according to their mRNA-based subtypes and found that the mesenchymal tumors had significantly decreased miR-181 family expression compared with the other three subtypes while the proneural subtype harbored extremely high miR-181 family expression. Patients with high miR-181 family expression had longer overall survival (p = 0.0031). We also confirmed that NF-κB-targeting genes and the EMT (epithelial-mesenchymal transition) pathway were inversely correlated with miR-181 family expression and that the entire miR-181 family inhibited glioma cell invasion and proliferation; of these, miR-181b was the most effective suppressor. Furthermore, miR-181b was validated to suppress EMT by targeting KPNA4 and was associated with survival outcome in the TCGA and CGGA datasets and in another independent cohort. The EMT-inhibitory effect of miR-181b was lost after KPNA4 expression was restored. We also identified the antitumorigenic activity of miR-181b in vitro and in vivo. Our results showed that miR-181 family expression was closely correlated with TCGA subtypes and patients’ overall survival, indicating that miR-181b, a tumor-suppressive miRNA, could be a novel therapeutic candidate for treating gliomas. Nature Publishing Group 2015-08-18 /pmc/articles/PMC4539550/ /pubmed/26283154 http://dx.doi.org/10.1038/srep13072 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Wang, Hongjun Tao, Tao Yan, Wei Feng, Yan Wang, Yongzhi Cai, Jinquan You, Yongping Jiang, Tao Jiang, Chuanlu Upregulation of miR-181s reverses mesenchymal transition by targeting KPNA4 in glioblastoma |
title | Upregulation of miR-181s reverses mesenchymal transition by targeting KPNA4 in glioblastoma |
title_full | Upregulation of miR-181s reverses mesenchymal transition by targeting KPNA4 in glioblastoma |
title_fullStr | Upregulation of miR-181s reverses mesenchymal transition by targeting KPNA4 in glioblastoma |
title_full_unstemmed | Upregulation of miR-181s reverses mesenchymal transition by targeting KPNA4 in glioblastoma |
title_short | Upregulation of miR-181s reverses mesenchymal transition by targeting KPNA4 in glioblastoma |
title_sort | upregulation of mir-181s reverses mesenchymal transition by targeting kpna4 in glioblastoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539550/ https://www.ncbi.nlm.nih.gov/pubmed/26283154 http://dx.doi.org/10.1038/srep13072 |
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