Transcriptomic evaluation in pediatric spinal ependymoma reveals distinct molecular signatures.
Oncotarget. 2017 Dec 29;eight(70):115570-115581
Authors: Lourdusamy A, Luo LZ, Storer LC, Cohen KJ, Resar L, Grundy RG
Pediatric spinal ependymomas (SEPN) are necessary albeit unusual malignant central nervous system tumors with restricted remedy choices. Our present information concerning the underlying biology of those tumors is proscribed attributable to their rarity. To start to elucidate molecular mechanisms that give rise to pediatric SEPN, we in contrast the transcriptomic panorama of SEPNs to that of intracranial ependymomas utilizing genome-wide mRNA and microRNA (miRNA) expression profiling in main tumour samples. We discovered that pediatric SEPNs are characterised by elevated expression of genes concerned in developmental processes, oxidative phosphorylation, mobile respiration, electron transport chain, and cofactor metabolic course of. Subsequent, we in contrast pediatric spinal and intracranial ependymomas with the identical tumours in adults and located a comparatively low variety of genes in pediatric tumours that had been shared with grownup tumours (12.5%). In distinction to grownup SEPN, down-regulated genes in pediatric SEPN weren’t enriched for place on chromosome 22. On the miRNA degree, we discovered ten miRNAs that had been perturbed in pediatric SEPN and we recognized regulatory relationships between these miRNAs and their putative targets mRNAs utilizing the integrative miRNA-mRNA community and predicted miRNA goal evaluation. These miRNAs embrace the oncomiR hsa-miR-10b and its member of the family hsa-miR-10a, each of that are upregulated and goal chromatin modification genes which might be down regulated in pediatric SEPN. The tumor suppressor, hsa-miR-124, was down regulated in pediatric SEPN and it usually represses genes concerned in cell-cell communication and metabolic processes. Collectively, our findings counsel that pediatric SEPN is characterised by a definite transcriptional panorama from that of pediatric intracranial EPNs or grownup tumors (each SEPNs and intracranial EPNs). Though confirmatory research are wanted, our research reveals novel molecular pathways which will drive tumorigenesis and will function biomarkers or rational therapeutic targets.
PMID: 29383182 [PubMed]