ŠÁNA, Jiří, Andrej BEŠŠE, Jakub ONDRÁČEK, Marek VEČEŘA, Pavel FADRUS, Leoš KŘEN, Hana MLČOCHOVÁ, Robert ILIEV, Jitka MLČOCHOVÁ, Petra VYCHYTILOVÁ, Renata HÉŽOVÁ, Jaroslav JURÁČEK and Ondřej SLABÝ. MiRNA-31-5p expression in glioblastoma tissue and effects of its replacement in glioblastoma cells. In 106th Annual Meeting of the American Association for Cancer Research 2015, Philadelphia. 2015. ISSN 0008-5472.
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Basic information
Original name MiRNA-31-5p expression in glioblastoma tissue and effects of its replacement in glioblastoma cells
Authors ŠÁNA, Jiří, Andrej BEŠŠE, Jakub ONDRÁČEK, Marek VEČEŘA, Pavel FADRUS, Leoš KŘEN, Hana MLČOCHOVÁ, Robert ILIEV, Jitka MLČOCHOVÁ, Petra VYCHYTILOVÁ, Renata HÉŽOVÁ, Jaroslav JURÁČEK and Ondřej SLABÝ.
Edition 106th Annual Meeting of the American Association for Cancer Research 2015, Philadelphia, 2015.
Other information
Original language English
Type of outcome Conference abstract
Field of Study 30200 3.2 Clinical medicine
Country of publisher United States of America
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 8.556
Organization unit Central European Institute of Technology
ISSN 0008-5472
Keywords in English miR-31-5p; glioblastoma multiforme; in vitro analyses
Tags International impact, Reviewed
Changed by Changed by: Mgr. Petra Vychytilová, Ph.D., učo 211789. Changed: 22/10/2015 19:36.
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
ED1.1.00/02.0068, research and development projectName: CEITEC - central european institute of technology
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
NT13860, research and development projectName: Studium signální dráhy EGFR a expresních profilů mikroRNA v predikci odpovědi na cílenou anti-EGFR terapii u pacientů s kolorektálním karcinomem s nemutovanou variantou onkogenu KRAS
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