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

• DOI: 10.1007/s13277-015-4654-x
• Publication Date: 2015-12-21T14:56:33Z
• Authors: Andrej Besse; Jiri Sana; Radek Lakomy; Leos Kren; Pavel Fadrus; Martin Smrcka; Marketa Hermanova; Radim Jancalek; Stefan Reguli; Radim Lipina; Marek Svoboda; Pavel Slampa; Ondrej Slaby
• Keywords: Male; Brain Neoplasms; Gene Expression Profiling; Neuropeptides; Membrane Proteins; Cell Cycle Checkpoints; Middle Aged; Neoplasm Proteins; Gene Expression Regulation, Neoplastic; MicroRNAs; Cell Line, Tumor; Humans; Female; Protein Phosphatase 2; RNA, Neoplasm; Carrier Proteins; Glioblastoma; Cell Division; DNA Damage; Monomeric GTP-Binding Proteins

Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor. Despite radical surgery and radiotherapy supported by chemotherapy, disease still remains incurable with an extremely low median survival rate 12-15 months from time initial diagnosis. The main cause treatment failure considered to be presence cells that are resistant treatment. MicroRNAs (miRNAs) as regulators gene expression involved in tumor pathogenesis, including GBM. MiR-338 a brain-specific miRNA which has been described target pathways proliferation differentiation. In our study, miR-338-3p miR-338-5p were differentially expressed GBM tissue comparison non-tumor tissue. Overexpression mimic did not show any changes rates cell lines (A172, T98G, U87MG). On other hand, pre-miR-338-5p notably decreased caused cycle arrest. Since radiation currently modality GBM, we combined overexpression radiation, led significantly proliferation, increased arrest, apoptosis irradiation-only cells. To better elucidate mechanism action, performed profiling analysis revealed targets being Ndfip1, Rheb, ppp2R5a. These genes have DNA damage response, regulation. knowledge, this first study describe role its potential improve sensitivity radiation.