@article{e121b2e53567453e818478ef554a98f8,
title = "The transcribed ultraconserved region uc.160+ enhances processing and A-to-I editing of the miR-376 cluster: hypermethylation improves glioma prognosis",
abstract = "Transcribed 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.",
keywords = "A-to-I editing, APOPTOSIS, EXPRESSION, MICRORNAS, NONCODING RNA, PROVIDES, RYBP INTERACTS, T-UCR, glioma, miR-376, noncoding RNA, pri-miRNA biogenesis",
author = "M. Soler and V. Davalos and A. Sanchez-Castillo and C. Mora-Martinez and F. Setien and E. Siqueira and {de Moura}, M.C. and M. Esteller and S. Guil",
note = "Funding Information: We thank the CERCA program (Generalitat de Catalunya) and the Josep Carreras Foundation for institutional support. This work was supported by the Ministerio de Ciencia e Innovaci{\'o}n (MCI)—Agencia Estatal de Investigaci{\'o}n (AEI) and the Instituto de Salud Carlos III (ISCIII), cofinanced by the European Development Regional Fund, {\textquoteleft}A way to achieve Europe{\textquoteright} ERDF, under grant numbers PID2019‐111658RB‐I00 (SG), RTI2018‐094049‐B‐I00 {\textquoteleft}EPIRNA{\textquoteright} (ME), and the Health and Science Departments of the Catalan Government (Generalitat de Catalunya). ME is an ICREA Research Professor. Funding Information: We thank the CERCA program (Generalitat de Catalunya) and the Josep Carreras Foundation for institutional support. This work was supported by the Ministerio de Ciencia e Innovaci{\'o}n (MCI)—Agencia Estatal de Investigaci{\'o}n (AEI) and the Instituto de Salud Carlos III (ISCIII), cofinanced by the European Development Regional Fund, {\textquoteleft}A way to achieve Europe{\textquoteright} ERDF, under grant numbers PID2019-111658RB-I00 (SG), RTI2018-094049-B-I00 {\textquoteleft}EPIRNA{\textquoteright} (ME), and the Health and Science Departments of the Catalan Government (Generalitat de Catalunya). ME is an ICREA Research Professor. Publisher Copyright: {\textcopyright} 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies",
year = "2022",
month = feb,
doi = "10.1002/1878-0261.13121",
language = "English",
volume = "16",
pages = "648--664",
journal = "Molecular oncology",
issn = "1574-7891",
publisher = "John Wiley & Sons Inc.",
number = "3",
}