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MiR-338-5p sensitizes glioblastoma cells to radiation through regulation of genes involved in DNA damage response

Besse, Andrej
Author Besse, Andrej Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Faculty of Medicine, Masaryk University, Brno, Czech Republic Central European Institute of Technology (CEITEC), Masaryk University, University Campus Bohunice, Building A3, Kamenice 5, 625 00, Brno, Czech Republic
Sana, Jiri
Author Sana, Jiri Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Faculty of Medicine, Masaryk University, Brno, Czech Republic Central European Institute of Technology (CEITEC), Masaryk University, University Campus Bohunice, Building A3, Kamenice 5, 625 00, Brno, Czech Republic
Lakomy, Radek
Author Lakomy, Radek Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Faculty of Medicine, Masaryk University, Brno, Czech Republic
Kren, Leos
Author Kren, Leos University Hospital Brno, Department of Pathology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
Fadrus, Pavel
Author Fadrus, Pavel University Hospital Brno, Department of Neurosurgery, Faculty of Medicine, Masaryk University, Brno, Czech Republic
Smrcka, Martin
Author Smrcka, Martin University Hospital Brno, Department of Neurosurgery, Faculty of Medicine, Masaryk University, Brno, Czech Republic
Hermanova, Marketa
Author Hermanova, Marketa First Department of Pathological Anatomy, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic
Jancalek, Radim
Author Jancalek, Radim Department of Neurosurgery, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic
Reguli, Stefan
Author Reguli, Stefan Department of Neurosurgery, University Hospital Ostrava, Ostrava, Czech Republic
Lipina, Radim
Author Lipina, Radim Department of Neurosurgery, University Hospital Ostrava, Ostrava, Czech Republic
Svoboda, Marek
Author Svoboda, Marek Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Faculty of Medicine, Masaryk University, Brno, Czech Republic
Slampa, Pavel
Author Slampa, Pavel Department of Radiation Oncology, Memorial Cancer Institute, Brno, Czech Republic
Slaby, Ondrej
Author Slaby, Ondrej Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Faculty of Medicine, Masaryk University, Brno, Czech Republic. on.slaby@gmail.com Central European Institute of Technology (CEITEC), Masaryk University, University Campus Bohunice, Building A3, Kamenice 5, 625 00, Brno, Czech Republic. on.slaby@gmail.com

Tumour biology. 2016 Jun ; 37 (6) : 7719-27. [epub] 20151221

Tumour Biol
ISSN 1423-0380 | 1010-4283
Source

Language English Country United States Media print-electronic

Document type Journal Article

Persistent link https://www.medvik.cz/link/pmid26692101

PubMed 26692101
DOI 10.1007/s13277-015-4654-x
PII: 10.1007/s13277-015-4654-x
Knihovny.cz E-resources

Keywords
GBM, Glioblastoma multiforme, Radiation resistance, miRNA, miRNA338-5p,
MeSH
Cell Division drug effects radiation effects MeSH
Glioblastoma genetics pathology MeSH
Cell Cycle Checkpoints drug effects radiation effects MeSH
Middle Aged MeSH
Humans MeSH
Membrane Proteins biosynthesis genetics MeSH
MicroRNAs genetics MeSH
Monomeric GTP-Binding Proteins biosynthesis genetics MeSH
Cell Line, Tumor MeSH
Neoplasm Proteins biosynthesis genetics MeSH
Brain Neoplasms genetics pathology MeSH
Neuropeptides biosynthesis genetics MeSH
DNA Damage genetics MeSH
Ras Homolog Enriched in Brain Protein MeSH
Protein Phosphatase 2 biosynthesis genetics MeSH
Gene Expression Regulation, Neoplastic genetics MeSH
RNA, Neoplasm genetics MeSH
Gene Expression Profiling MeSH
Radiation Tolerance genetics MeSH
Carrier Proteins biosynthesis genetics MeSH
Check Tag
Middle Aged MeSH
Humans MeSH
Male MeSH
Female MeSH
Publication type
Journal Article MeSH
Names of Substances
Membrane Proteins MeSH
MicroRNAs MeSH
MIRN338 microRNA, human MeSH Browser
Monomeric GTP-Binding Proteins MeSH
Neoplasm Proteins MeSH
NDFIP1 protein, human MeSH Browser
Neuropeptides MeSH
PPP2R5A protein, human MeSH Browser
Ras Homolog Enriched in Brain Protein MeSH
Protein Phosphatase 2 MeSH
RHEB protein, human MeSH Browser
RNA, Neoplasm MeSH
Carrier Proteins 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.

1st Department of Pathological Anatomy St Anne's University Hospital and Faculty of Medicine Masaryk University Brno Czech Republic

Central European Institute of Technology Masaryk University University Campus Bohunice Building A3 Kamenice 5 625 00 Brno Czech Republic

Department of Neurosurgery St Anne's University Hospital and Faculty of Medicine Masaryk University Brno Czech Republic

Department of Neurosurgery University Hospital Ostrava Ostrava Czech Republic

Department of Radiation Oncology Memorial Cancer Institute Brno Czech Republic

Masaryk Memorial Cancer Institute Department of Comprehensive Cancer Care Faculty of Medicine Masaryk University Brno Czech Republic

University Hospital Brno Department of Neurosurgery Faculty of Medicine Masaryk University Brno Czech Republic

University Hospital Brno Department of Pathology Faculty of Medicine Masaryk University Brno Czech Republic

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