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 language | English |
|---|---|
| Pages (from-to) | 1512-1525 |
| Number of pages | 14 |
| Journal | FEBS Journal |
| Volume | 282 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2015 Apr 1 |
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Keywords
- CBL-B
- EGFR
- invasion
- miR-30e
- MMP-2
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
Cite this
Ionizing radiation-inducible miR-30e promotes glioma cell invasion through EGFR stabilization by directly targeting CBL-B. / Kwak, Seo Young; Kim, Bu Yeon; Ahn, Hyun Joo; Yoo, Je Ok; Kim, Joon; Bae, In Hwa; Han, Young Hoon.
In: FEBS Journal, Vol. 282, No. 8, 01.04.2015, p. 1512-1525.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ionizing radiation-inducible miR-30e promotes glioma cell invasion through EGFR stabilization by directly targeting CBL-B
AU - Kwak, Seo Young
AU - Kim, Bu Yeon
AU - Ahn, Hyun Joo
AU - Yoo, Je Ok
AU - Kim, Joon
AU - Bae, In Hwa
AU - Han, Young Hoon
PY - 2015/4/1
Y1 - 2015/4/1
N2 - 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.
AB - 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.
KW - CBL-B
KW - EGFR
KW - invasion
KW - miR-30e
KW - MMP-2
UR - http://www.scopus.com/inward/record.url?scp=84927636684&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84927636684&partnerID=8YFLogxK
U2 - 10.1111/febs.13238
DO - 10.1111/febs.13238
M3 - Article
C2 - 25691332
AN - SCOPUS:84927636684
VL - 282
SP - 1512
EP - 1525
JO - FEBS Journal
JF - FEBS Journal
SN - 1742-464X
IS - 8
ER -