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miR-219-5p Inhibits Receptor Tyrosine Kinase Pathway by Targeting EGFR in Glioblastoma
Glioblastoma is one of the common types of primary brain tumors with a median survival of 12–15 months. The receptor tyrosine kinase (RTK) pathway is known to be deregulated in 88% of the patients with glioblastoma. 45% of GBM patients show amplifications and activating mutations in EGFR gene leadin...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656853/ https://www.ncbi.nlm.nih.gov/pubmed/23690991 http://dx.doi.org/10.1371/journal.pone.0063164 |
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author | Rao, Soumya Alige Mahabala Arimappamagan, Arivazhagan Pandey, Paritosh Santosh, Vani Hegde, Alangar Sathyaranjandas Chandramouli, Bangalore Ashwathnarayanara Somasundaram, Kumaravel |
author_facet | Rao, Soumya Alige Mahabala Arimappamagan, Arivazhagan Pandey, Paritosh Santosh, Vani Hegde, Alangar Sathyaranjandas Chandramouli, Bangalore Ashwathnarayanara Somasundaram, Kumaravel |
author_sort | Rao, Soumya Alige Mahabala |
collection | PubMed |
description | Glioblastoma is one of the common types of primary brain tumors with a median survival of 12–15 months. The receptor tyrosine kinase (RTK) pathway is known to be deregulated in 88% of the patients with glioblastoma. 45% of GBM patients show amplifications and activating mutations in EGFR gene leading to the upregulation of the pathway. In the present study, we demonstrate that a brain specific miRNA, miR-219-5p, repressed EGFR by directly binding to its 3′-UTR. The expression of miR-219-5p was downregulated in glioblastoma and the overexpression of miR-219-5p in glioma cell lines inhibited the proliferation, anchorage independent growth and migration. In addition, miR-219-5p inhibited MAPK and PI3K pathways in glioma cell lines in concordance with its ability to target EGFR. The inhibitory effect of miR-219-5p on MAPK and PI3K pathways and glioma cell migration could be rescued by the overexpression of wild type EGFR and vIII mutant of EGFR (both lacking 3′-UTR and thus being insensitive to miR-219-5p) suggesting that the inhibitory effects of miR-219-5p were indeed because of its ability to target EGFR. We also found significant negative correlation between miR-219-5p levels and total as well as phosphorylated forms of EGFR in glioblastoma patient samples. This indicated that the downregulation of miR-219-5p in glioblastoma patients contribute to the increased activity of the RTK pathway by the upregulation of EGFR. Thus, we have identified and characterized miR-219-5p as the RTK regulating novel tumor suppressor miRNA in glioblastoma. |
format | Online Article Text |
id | pubmed-3656853 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-36568532013-05-20 miR-219-5p Inhibits Receptor Tyrosine Kinase Pathway by Targeting EGFR in Glioblastoma Rao, Soumya Alige Mahabala Arimappamagan, Arivazhagan Pandey, Paritosh Santosh, Vani Hegde, Alangar Sathyaranjandas Chandramouli, Bangalore Ashwathnarayanara Somasundaram, Kumaravel PLoS One Research Article Glioblastoma is one of the common types of primary brain tumors with a median survival of 12–15 months. The receptor tyrosine kinase (RTK) pathway is known to be deregulated in 88% of the patients with glioblastoma. 45% of GBM patients show amplifications and activating mutations in EGFR gene leading to the upregulation of the pathway. In the present study, we demonstrate that a brain specific miRNA, miR-219-5p, repressed EGFR by directly binding to its 3′-UTR. The expression of miR-219-5p was downregulated in glioblastoma and the overexpression of miR-219-5p in glioma cell lines inhibited the proliferation, anchorage independent growth and migration. In addition, miR-219-5p inhibited MAPK and PI3K pathways in glioma cell lines in concordance with its ability to target EGFR. The inhibitory effect of miR-219-5p on MAPK and PI3K pathways and glioma cell migration could be rescued by the overexpression of wild type EGFR and vIII mutant of EGFR (both lacking 3′-UTR and thus being insensitive to miR-219-5p) suggesting that the inhibitory effects of miR-219-5p were indeed because of its ability to target EGFR. We also found significant negative correlation between miR-219-5p levels and total as well as phosphorylated forms of EGFR in glioblastoma patient samples. This indicated that the downregulation of miR-219-5p in glioblastoma patients contribute to the increased activity of the RTK pathway by the upregulation of EGFR. Thus, we have identified and characterized miR-219-5p as the RTK regulating novel tumor suppressor miRNA in glioblastoma. Public Library of Science 2013-05-17 /pmc/articles/PMC3656853/ /pubmed/23690991 http://dx.doi.org/10.1371/journal.pone.0063164 Text en © 2013 Rao 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 Rao, Soumya Alige Mahabala Arimappamagan, Arivazhagan Pandey, Paritosh Santosh, Vani Hegde, Alangar Sathyaranjandas Chandramouli, Bangalore Ashwathnarayanara Somasundaram, Kumaravel miR-219-5p Inhibits Receptor Tyrosine Kinase Pathway by Targeting EGFR in Glioblastoma |
title | miR-219-5p Inhibits Receptor Tyrosine Kinase Pathway by Targeting EGFR in Glioblastoma |
title_full | miR-219-5p Inhibits Receptor Tyrosine Kinase Pathway by Targeting EGFR in Glioblastoma |
title_fullStr | miR-219-5p Inhibits Receptor Tyrosine Kinase Pathway by Targeting EGFR in Glioblastoma |
title_full_unstemmed | miR-219-5p Inhibits Receptor Tyrosine Kinase Pathway by Targeting EGFR in Glioblastoma |
title_short | miR-219-5p Inhibits Receptor Tyrosine Kinase Pathway by Targeting EGFR in Glioblastoma |
title_sort | mir-219-5p inhibits receptor tyrosine kinase pathway by targeting egfr in glioblastoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656853/ https://www.ncbi.nlm.nih.gov/pubmed/23690991 http://dx.doi.org/10.1371/journal.pone.0063164 |
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