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243357.pdf (1.32 MB)

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2021-10-19

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cc-by (c) Soler, M. et al., 2021
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/221181

The transcribed ultraconserved region uc.160+ enhances processing and A-to-I editing of the miR-376 cluster: hypermethylation improves glioma prognosis

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Recurs relacionat

https://doi.org/10.1002/1878-0261.13121

Resum

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.

Matèries

Estructura molecular, ADN, Glioma

Matèries (anglès)

Molecular structure, DNA, Gliomas

Citació

Col·leccions

Articles publicats en revistes (Ciències Fisiològiques)

Citació

SOLER, Marta, et al. The transcribed ultraconserved region uc.160+ enhances processing and A-to-I editing of the miR-376 cluster: hypermethylation improves glioma prognosis. Molecular Oncology. 2021. Vol. 16, num. 3, pags. 648-664. ISSN 1574-7891. [consulted: 19 of August of 2026]. Available at: https://hdl.handle.net/2445/221181

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