Genome-wide profiling of lncRNAs in pediatric intracranial ependymomas identifies H19 as a novel pathogenic driver.
AI interpretation is pending for this paper.
Open original publication →What the AI sees
Not AI summarized yet.
Research significance
Pending deeper interpretation.
Source abstract
BACKGROUND: Pediatric ependymomas (EPNs) frequently develop in the cerebellum and are treated with non-targeted therapies, partly due to limited understanding of their pathobiology. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis but remain mostly unexplored in pediatric EPNs. This study aimed to identify novel oncogenic drivers and prognostic biomarkers in posterior fossa (PF) EPN by profiling the genome-wide lncRNA expression landscape. METHODS: We used RNA sequencing data from 13 samples (3 controls and 10 PF EPNs) to profile the lncRNA expression landscape. Perturbation and functional assays in EPN cell lines were used to investigate putative oncogenic drivers, while large public datasets were used to explore associations with prognosis. RESULTS: We identified several aberrantly expressed lncRNAs, including IGF2-AS, CD44-DT, and HOTAIRM1 and lncRNAs associated with poor prognosis such as DELEC1, H19, and CD44-AS1. We focused on H19 and IGF2-AS, which reside in the same imprinted locus together with IGF2, a gene encoding a growth factor. Knockdown of H19 reduced expression of cell cycle-related genes, decreased cell viability, and increased apoptosis and cell cycle arrest. In contrast, IGF2-AS knockdown upregulated H19 and the expression of cell cycle-related genes. Finally, public data showed that H19 is more abundant in the EPN PF subgroup A, and that methylation of its imprinting control region (ICR) correlates strongly with better prognosis in EPN PF subgroup B (PFB). CONCLUSION: These findings suggest that H19 plays an oncogenic role in EPN and that the methylation status of its ICR may serve as a prognostic biomarker in PFB.