ArticleNeuro-oncology advances
Systematic decoding the functional role of human endogenous retrovirus-derived RNAs in medulloblastoma.
Article in Neuro-oncology advances. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Medulloblastoma (MB) is the most common malignant pediatric brain tumor, but its pathogenesis remains poorly understood. Although human endogenous retrovirus-derived RNAs (hervRNAs) are implicated in tumorigenesis across various cancers, their functional role in the pathogenesis of MB has not been discovered. Methods: We collected total RNA samples from 63 pediatric MB patients for RNA sequencing and identified the expression of hervRNAs in a locus-specific manner. The functional role of hervRNAs was analyzed through independent expression analysis, gene set enrichment analysis, weighted correlation network analysis, and further validated by siRNA-knockdown experiment in D283 cells. Results: We systematically identified 39,613 MB-expressed hervRNAs and found that their expression profile could distinguish the four consensus molecular subgroups. Specifically, 145 subgroup-specific hervRNAs were identified to be significantly associated with tumor development. Functional annotation revealed that these hervRNAs were enriched in known MB subgroup-related pathways but also implied novel pathways related to regulated necrosis, negative regulation of class C GPCR, extracellular matrix remodeling, as well as DNA methylation. Notably, the expression of Group3-specific hervRNAs showed a significant negative correlation with promoter DNA methylation levels. Experimental validation confirmed that Group3-specific Conclusion: Our work provided insights into MB tumorigenesis in the layer of hervRNA, uncovering potential targets for therapeutic intervention and novel biomarkers for molecular classification.
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