MiR-338-5p sensitizes glioblastoma cells to radiation through regulation of genes involved in DNA damage response
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články
PubMed
26692101
DOI
10.1007/s13277-015-4654-x
PII: 10.1007/s13277-015-4654-x
Knihovny.cz E-zdroje
- Klíčová slova
- GBM, Glioblastoma multiforme, Radiation resistance, miRNA, miRNA338-5p,
- MeSH
- buněčné dělení účinky léků účinky záření MeSH
- glioblastom genetika patologie MeSH
- kontrolní body buněčného cyklu účinky léků účinky záření MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránové proteiny biosyntéza genetika MeSH
- mikro RNA genetika MeSH
- monomerní proteiny vázající GTP biosyntéza genetika MeSH
- nádorové buněčné linie MeSH
- nádorové proteiny biosyntéza genetika MeSH
- nádory mozku genetika patologie MeSH
- neuropeptidy biosyntéza genetika MeSH
- poškození DNA genetika MeSH
- protein Rheb MeSH
- proteinfosfatasa 2 biosyntéza genetika MeSH
- regulace genové exprese u nádorů genetika MeSH
- RNA nádorová genetika MeSH
- stanovení celkové genové exprese MeSH
- tolerance záření genetika MeSH
- transportní proteiny biosyntéza genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- membránové proteiny MeSH
- mikro RNA MeSH
- MIRN338 microRNA, human MeSH Prohlížeč
- monomerní proteiny vázající GTP MeSH
- nádorové proteiny MeSH
- NDFIP1 protein, human MeSH Prohlížeč
- neuropeptidy MeSH
- PPP2R5A protein, human MeSH Prohlížeč
- protein Rheb MeSH
- proteinfosfatasa 2 MeSH
- RHEB protein, human MeSH Prohlížeč
- RNA nádorová MeSH
- transportní proteiny MeSH
Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor. Despite radical surgery and radiotherapy supported by chemotherapy, the disease still remains incurable with an extremely low median survival rate of 12-15 months from the time of initial diagnosis. The main cause of treatment failure is considered to be the presence of cells that are resistant to the treatment. MicroRNAs (miRNAs) as regulators of gene expression are involved in the tumor pathogenesis, including GBM. MiR-338 is a brain-specific miRNA which has been described to target pathways involved in proliferation and differentiation. In our study, miR-338-3p and miR-338-5p were differentially expressed in GBM tissue in comparison to non-tumor brain tissue. Overexpression of miR-338-3p with miRNA mimic did not show any changes in proliferation rates in GBM cell lines (A172, T98G, U87MG). On the other hand, pre-miR-338-5p notably decreased proliferation and caused cell cycle arrest. Since radiation is currently the main treatment modality in GBM, we combined overexpression of pre-miR-338-5p with radiation, which led to significantly decreased cell proliferation, increased cell cycle arrest, and apoptosis in comparison to irradiation-only cells. To better elucidate the mechanism of action, we performed gene expression profiling analysis that revealed targets of miR-338-5p being Ndfip1, Rheb, and ppp2R5a. These genes have been described to be involved in DNA damage response, proliferation, and cell cycle regulation. To our knowledge, this is the first study to describe the role of miR-338-5p in GBM and its potential to improve the sensitivity of GBM to radiation.
Department of Neurosurgery University Hospital Ostrava Ostrava Czech Republic
Department of Radiation Oncology Memorial Cancer Institute Brno Czech Republic
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