title: Ionizing radiation-inducible miR-30e promotes glioma cell invasion through EGFR stabilization by directly targeting CBL-B.
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.
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea; Laboratory of Biochemistry, School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Seo-Young
authors.initials: SY
authors.lastname: Kwak
authors.forename: Bu-Yeon
authors.initials: BY
authors.lastname: Kim
authors.forename: Hyun-Joo
authors.initials: HJ
authors.lastname: Ahn
authors.forename: Je-Ok
authors.initials: JO
authors.lastname: Yoo
authors.forename: Joon
authors.initials: J
authors.lastname: Kim
authors.forename: In Hwa
authors.initials: IH
authors.lastname: Bae
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Han
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000528:radiation effects*; D009361:Neoplasm Invasiveness; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011839:Radiation, Ionizing; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D054875:Ubiquitination; D014945:Wound Healing
chemical_list: D020413:3' Untranslated Regions; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D050721:Proto-Oncogene Proteins c-cbl; C512478:EGFR protein, human; D066246:ErbB Receptors; C067419:CBL protein, human
keywords: CBL-B; EGFR; MMP-2; invasion; miR-30e