Rao, Soumya Alige Mahabala and Arimappamagan, Arivazhagan and Pandey, Paritosh and Santosh, Vani and Hegde, Alangar Sathyaranjandas and Chandramouli, Bangalore Ashwathnarayanara and Somasundaram, Kumaravel (2013) miR-219-5p inhibits receptor tyrosine kinase pathway by targeting EGFR in glioblastoma. In: PLOS One, 8 (5). e63164_1-e63164_10.
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Abstract
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.
| Item Type: | Journal Article |
|---|---|
| Publication: | PLOS One |
| Publisher: | Public Library of Science |
| Additional Information: | Copyright of this article belongs to Public Library of Science. |
| Department/Centre: | Division of Biological Sciences > Microbiology & Cell Biology |
| Date Deposited: | 11 Jul 2013 06:25 |
| Last Modified: | 03 Nov 2018 08:42 |
| URI: | http://eprints.iisc.ac.in/id/eprint/46819 |
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