SLABÝ, Ondřej, Jiří ŠÁNA, Andrej BEŠŠE, Jakub ONDRÁČEK, Marek VEČEŘA, Pavel FADRUS, Leoš KŘEN, Soňa KRYŠTOFOVÁ and Martin SMRČKA. MiRNA-31-5p expression in glioblastoma tissue and effects of its replacement in glioblastoma cells. In Brněnské neurochirurgické dny. 2015.
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Basic information
Original name MiRNA-31-5p expression in glioblastoma tissue and effects of its replacement in glioblastoma cells
Authors SLABÝ, Ondřej (203 Czech Republic, belonging to the institution), Jiří ŠÁNA (203 Czech Republic, belonging to the institution), Andrej BEŠŠE (703 Slovakia, belonging to the institution), Jakub ONDRÁČEK (203 Czech Republic, belonging to the institution), Marek VEČEŘA (703 Slovakia, belonging to the institution), Pavel FADRUS (203 Czech Republic, belonging to the institution), Leoš KŘEN (203 Czech Republic, belonging to the institution), Soňa KRYŠTOFOVÁ (203 Czech Republic, belonging to the institution) and Martin SMRČKA (203 Czech Republic, guarantor, belonging to the institution).
Edition Brněnské neurochirurgické dny, 2015.
Other information
Original language English
Type of outcome Conference abstract
Field of Study 30200 3.2 Clinical medicine
Country of publisher Czech Republic
Confidentiality degree is not subject to a state or trade secret
RIV identification code RIV/00216224:14110/15:00087475
Organization unit Faculty of Medicine
Keywords in English MiRNA-31-5p; glioblastoma
Tags EL OK, podil
Changed by Changed by: Ing. Mgr. Věra Pospíšilíková, učo 9005. Changed: 22. 1. 2016 15:48.
Abstract
Introduction: Glioblastoma multiforme (GBM) is the most malignant primary tumor of the central nervous system of adults. Our previous study has showed significant alterations in expression of microRNAs (miRNAs) in GBM tissue. Some of these miRNAs were also correlated with overall survival, whereas miR-31-5p was the most significant, indicating its tumor suppressive functioning. In this study, miR-31-5p was studied on larger cohort of GBM patients and also in vitro of selected GBM cell lines. Patients, Cell lines and Methods: Expression of miR-31-5p was validated on cohort of 58 GBM patients and 10 samples of non-tumor brain tissue. We have increased expression level of miR-31-5p using transient transfection of specific miRNA mimic in GBM cell lines A172, U87MG, T98MG, and U251. Cell viability and proliferation were analyzed using MTT assay and cell counting, respectively. Cell cycle analyses were performed by flow-cytometry using propidium iodide. Migration and invasion potential were measured by the wound healing assay and transwell invasion assay, respectively. Finally, potential targets of miR-31-5p were discovered using combination of bioinformatics algorithms for target prediction and GeneChip Human Gene 2.0 ST Array (Affymetrix) whole-genome expression profiling. Results: Down-regulation of miR-31-5p was successfully validated on cohort of 58 GBM patients and 10 samples of non-tumor brain tissue (p<0.001). MiR-31-5p was significantly associated also with progression-free and overall survival of GBM patients. Transient expression of miR-31-5p led to the significant decrease of GBM cell proliferation and viability in A172, U87MG, T98G, and U251 cell lines (t-test; p < 0.05) due to the cell cycle arrest in G1 phase. Moreover, transfected A172 and U251 cells had a lower migration and invasiveness potential in comparison with control cells (t-test; p < 0.05). Finally, analysis of global gene expression profiles together with predicted mRNA targets revealed several interesting targets of miR-31-5p, which are involved in crucial signaling pathways of GBM. Conclusion: Taken together, our data suggest that miR-31-5p is not only powerful diagnostic marker as showed previously but seems to be promising therapeutic target in GBM patients.
Links
NT13514, research and development projectName: Analýza mikroRNA v glioblastomových kmenových buňkách: predikce léčebné odpovědi a identifikace nových terapeutických cílů u pacientů s glioblastomem
NT13547, research and development projectName: Studium mikroRNA a genů asociovaných s procesem epiteliálně-mezenchymální tranzice jako potenciálních markerů pro predikci rizika a časný záchyt metastazování u pacientů s renálním karcinomem
NT13549, research and development projectName: Vytvoření diagnostické sady cirkulujících mikroRNA pro neinvazivní časnou diagnostiku a sledování pacientů s kolorektálním karcinomem
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