MicroRNAs are endogenously expressed regulatory noncoding RNAs. Altered expression levels of several microRNAs have been observed in glioblastomas. Functions and direct mRNA targets for these microRNAs have been relatively well studied over the last years. According to these data, it is now evident, that impairment of microRNA regulatory network is one of the key mechanisms in glioblastoma pathogenesis. MicroRNA deregulation is involved in processes such as cell proliferation, apoptosis, cell cycle regulation, invasion, glioma stem cell behavior, and angiogenesis. In this review, we summarize the current knowledge of miRNA functions in glioblastoma with an emphasis on its significance in glioblastoma oncogenic signaling and its potential to serve as a disease biomarker and a novel therapeutic target in oncology.

• MeSH
• glioblastom metabolismus   MeSH
• lidé MeSH
• mikro RNA klasifikace   genetika   fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• mikro RNA 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.

• 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