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miR-219-5p inhibits receptor tyrosine kinase pathway by targeting EGFR in glioblastoma

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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Official URL: http://dx.doi.org/10.1371/journal.pone.0063164

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
Additional Information: Copyright of this article belongs to Public Library of Science.
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Depositing User: Francis Jayakanth
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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