Premium
Ionizing radiation‐inducible miR‐30e promotes glioma cell invasion through EGFR stabilization by directly targeting CBL ‐B
Author(s) -
Kwak SeoYoung,
Kim BuYeon,
Ahn HyunJoo,
Yoo JeOk,
Kim Joon,
Bae In Hwa,
Han YoungHoon
Publication year - 2015
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13238
Subject(s) - protein kinase b , ubiquitin ligase , ectopic expression , epidermal growth factor receptor , biology , cancer research , microbiology and biotechnology , signal transduction , rna , chemistry , ubiquitin , gene , receptor , biochemistry
Micro RNA s (mi RNA s) are small non‐coding RNA molecules that regulate gene expression at the transcriptional and post‐transcriptional levels. Here we show that miR‐30e, which was previously identified as an ionizing radiation‐inducible mi RNA , enhances cellular invasion by promoting secretion of the matrix metalloproteinase MMP ‐2. The enhancement of cellular invasion by miR‐30e involved up‐regulation of the epidermal growth factor receptor ( EGFR ) and subsequent activation of its downstream signaling mediators, AKT and extracellular signal‐regulated kinase . EGFR up‐regulation by miR‐30e occurred due to stabilization of the EGFR protein. The E3 ubiquitin ligase casitas B‐lineage lymphoma B ( CBL ‐B) was down‐regulated by miR‐30e, and this led to increased EGFR abundance. A 3′ UTR reporter assay confirmed that CBL ‐B is a direct target of miR‐30e. Knocking down CBL ‐B expression phenocopied the effects of miR‐30e, whereas ectopic expression of CBL ‐B suppressed miR‐30e‐induced EGFR up‐regulation and invasion. Collectively, our results suggest that targeting miR‐30e may limit the invasiveness induced during glioma radiotherapy.