Ionizing radiation-inducible miR-30e promotes glioma cell invasion through EGFR stabilization by directly targeting CBL-B

Seo Young Kwak, Bu Yeon Kim, Hyun Joo Ahn, Je Ok Yoo, Joon Kim, In Hwa Bae, Young Hoon Han

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) 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 miRNA, 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.

Original languageEnglish
Pages (from-to)1512-1525
Number of pages14
JournalFEBS Journal
Volume282
Issue number8
DOIs
Publication statusPublished - 2015 Apr 1

Keywords

  • CBL-B
  • EGFR
  • invasion
  • miR-30e
  • MMP-2

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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