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      Simultaneous miRNA and mRNA transcriptome profiling of glioblastoma samples reveals a novel set of OncomiR candidates and their target genes

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      Embargo Lift Date: 2019-12-01
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      Author(s)
      Güllüoğlu, Ş.
      Tüysüz, E. C.
      Şahin, M.
      Kuşkucu, A.
      Yaltırık, C. K.
      Türe, U.
      Küçükkaraduman, Barış
      Akbar, Muhammad Waqas
      Güre, Ali Osmay
      Bayrak, Ö. F.
      Dalan, A. B.
      Date
      2018
      Source Title
      Brain Research
      Print ISSN
      0006-8993
      Electronic ISSN
      1872-6240
      Publisher
      Elsevier
      Volume
      1700
      Pages
      199 - 210
      Language
      English
      Type
      Article
      Item Usage Stats
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      Abstract
      Although glioblastomas are common, there remains a need to elucidate the underlying mechanisms behind their initiation and progression and identify molecular pathways for improving treatment. In this study, sixteen fresh-frozen glioblastoma samples and seven samples of healthy brain tissues were analyzed with miRNA and whole transcriptome microarray chips. Candidate miRNAs and mRNAs were selected to validate expression in fifty patient samples in total with the criteria of abundance, relevance and prediction scores. miRNA and target mRNA relationships were assessed by inhibiting selected miRNAs in glioblastoma cells. Functional tests have been conducted in order to see the effects of miRNAs on invasion, migration and apoptosis of GBM cells. Analyses were carried out to determine correlations between selected molecules and clinicopathological features. 1332 genes and 319 miRNAs were found to be dysregulated by the microarrays. The results were combined and analyzed with Transcriptome Analysis Console 3 software and the DAVID online database. Primary differential pathways included Ras, HIF-1, MAPK signaling and cell adhesion. OncomiR candidates 21-5p, 92b-3p, 182-5p and 339-5p for glioblastoma negatively correlated with notable mRNA targets both in tissues and in in vitro experiments. miR-21-5p and miR-339-5p significantly affected migration, invasion and apoptosis of GBM cells in vitro. Significant correlations with overall survival, tumor volume, recurrence and age at diagnosis were discovered. In this article we present valuable integrated microarray analysis of glioblastoma samples regarding miRNA and gene-expression levels. Notable biomarkers and miRNA-mRNA interactions have been identified, some of which correlated with clinicopathological features in our cohort.
      Keywords
      Glioblastoma
      Microarray
      Mir-21-5p
      Mirna
      Prognosis
      Survival
      Permalink
      http://hdl.handle.net/11693/49842
      Published Version (Please cite this version)
      https://doi.org/10.1016/j.brainres.2018.08.035
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