Soler, MartaDavalos, VeronicaSánchez-Castillo, AnaísMora-Martinez, CarlosSetién, FernandoSiqueira, EdileneCastro de Moura, ManuelEsteller, Manel, 1968-Guil, Sonia2025-05-222025-05-222021-10-191574-7891https://hdl.handle.net/2445/221181Transcribed ultraconserved regions (T-UCRs) are noncoding RNAs derived from DNA sequences that are entirely conserved across species. Their expression is altered in many tumor types, and, although a role for T-UCRs as regulators of gene expression has been proposed, their functions remain largely unknown. Herein, we describe the epigenetic silencing of the uc.160+ T-UCR in gliomas and mechanistically define a novel RNA-RNA regulatory network in which uc.160+ modulates the biogenesis of several members of the miR-376 cluster. This includes the positive regulation of primary microRNA (pri-miRNA) cleavage and an enhanced A-to-I editing on its mature sequence. As a consequence, the expression of uc.160+ affects the downstream, miR-376-regulated genes, including the transcriptional coregulators RING1 and YY1-binding protein (RYBP) and forkhead box P2 (FOXP2). Finally, we elucidate the clinical impact of our findings, showing that hypermethylation of the uc.160+ CpG island is an independent prognostic factor associated with better overall survival in lower-grade gliomas, highlighting the importance of T-UCRs in cancer pathophysiology.17 p.application/pdfengcc-by (c) Soler, M. et al., 2021http://creativecommons.org/licenses/by/4.0/Estructura molecularADNGliomaMolecular structureDNAGliomasinfo:eu-repo/semantics/article7160922025-05-22info:eu-repo/semantics/openAccess34665919