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Abstract
Understanding pediatric brain tumor biology is essential to help on disease stratification, and to find novel markers for early diagnosis. MicroRNA (miRNA) expression has been linked to clinical outcomes and tumor biology. Here, we aimed to detect the expression of different miRNAs in different pediatric brain tumor subtypes to discover biomarkers for early detection and develop novel therapies. Expression of 82 miRNAs was detected in 120 pediatric brain tumors from fixed-formalin paraffin-embedded tissues, low-grade glioma, high-grade glioma, ependymoma, and medulloblastoma, using quantitative real-time PCR. Low-expression of miR-221, miR-9, and miR-181c/d and over-expression of miR-101, miR-222, miR-139, miR-1827, and miR-34c was found in medulloblastoma; low expression of miR-10a and over-expression of miR-10b and miR-29a in ependymoma; low expression of miR-26a and overexpression of miR-19a/b, miR-24, miR-27a, miR- 584, and miR-527 in low-grade glioma. Cox regression showed differential miRNA expression between responders and non-responders. The most specific were miR-10a and miR-29a low expression in LGG non-responders, miR-135a and miR-146b over-expression in ependymoma non-responders, and miR-135b overexpression in medulloblastoma non-responders. MicroRNAs are differentially expressed in subtypes of brain tumors suggesting that they may help diagnosis. A greater understanding of aberrant miRNA in pediatric brain tumors may support development of novel therapies.
Highlights
Pediatric brain tumors are the second most common pediatric malignancy, representing about 25% of all childhood cancers (Boman et al, 2009; Birks et al, 2011)
Patient samples miRNA expression was measured using quantitative RT-PCR in 120 samples from pediatric brain tumors (34 low grade glioma (LGG), 31 EPN, 30 MED, and 25 high grade glioma (HGG)); patients with the same disease were treated with the same protocol
To explore the importance of miRNAs in pediatric brain tumors, Formalin-fixed paraffin-embedded (FFPE) specimens of LGG, EPN, MED, and HGG were selected for miRNA expression using RT-quantitative polymerase chain reaction (qPCR)
Summary
Pediatric brain tumors are the second most common pediatric malignancy, representing about 25% of all childhood cancers (Boman et al, 2009; Birks et al, 2011). MiRNAs are small non-coding RNAs (18–25 nucleotides) that regulate gene expression in many cellular processes by affecting the post-transcriptional regulation (Bartel and Chen, 2004; Jonas and Izaurralde, 2015). During their biogenesis, miRNAs are transcribed to form hairpin structures called pri-miRNAs; the RNase III Drosha enzyme cleaves this structure in the nucleus to form precursor miRNAs (pre-miRNAs). The miRNAs have negative regulation of gene expression by binding the 3’ untranslated regions of mRNA of a protein-coding gene. MiRNA stability in bodily fluids, functionality in several tissue types, and their capability to detect early phase disease are all useful attributes (D’Urso et al, 2015; Stoicea et al, 2016)
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