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Título: | MicroRNA signature and integrative omics analyses define prognostic clusters and key pathways driving prognosis in patients with neuroendocrine neoplasms |
Autor: | Soldevilla, Beatriz CSIC ORCID; Lens-Pardo, Alberto; Espinosa-Olarte, Paula; Carretero-Puche, Carlos; Molina-Pinelo, Sonia CSIC ORCID; Robles, Carlos; Benavent, Marta CSIC ORCID; Gómez Izquierdo, Lourdes; Fierro-Fernández, Marta CSIC; Morales del Burgo, Patricia; Jiménez-Fonseca, Paula; Anton-Pascual, Beatriz; Rodríguez-Gil, Yolanda; Teijo-Quintans, Ana; La-Salvia, Anna; Rubio-Cuesta, Beatriz; Riesco-Martínez, María C.; García-Carbonero, Rocío CSIC ORCID | Palabras clave: | miRNAs NEN biology NEN patients Prognostic impact |
Fecha de publicación: | abr-2023 | Editor: | John Wiley & Sons Federation of European Biochemical Societies |
Citación: | Molecular Oncology 17(4): 582-597 (2023) | Resumen: | Neuroendocrine neoplasms (NENs) are mutationally quiet (low number of mutations/Mb), and epigenetic mechanisms drive their development and progression. We aimed at comprehensively characterising the microRNA (miRNA) profile of NENs, and exploring downstream targets and their epigenetic modulation. In total, 84 cancer-related miRNAs were analysed in 85 NEN samples from lung and gastroenteropancreatic (GEP) origin, and their prognostic value was evaluated by univariate and multivariate models. Transcriptomics (N = 63) and methylomics (N = 30) were performed to predict miRNA target genes, signalling pathways and regulatory CpG sites. Findings were validated in The Cancer Genome Atlas cohorts and in NEN cell lines. We identified a signature of eight miRNAs that stratified patients in three prognostic groups (5-year survival of 80%, 66% and 36%). Expression of the eight-miRNA gene signature correlated with 71 target genes involved in PI3K–Akt and TNFα–NF-kB signalling. Of these, 28 were associated with survival and validated in silico and in vitro. Finally, we identified five CpG sites involved in the epigenetic regulation of these eight miRNAs. In brief, we identified an 8-miRNA signature able to predict survival of patients with GEP and lung NENs, and identified genes and regulatory mechanisms driving prognosis in NEN patients. | Descripción: | © 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | Versión del editor: | https://doi.org/10.1002/1878-0261.13393 | URI: | http://hdl.handle.net/10261/351711 | DOI: | 10.1002/1878-0261.13393 | ISSN: | 1878-0261 |
Aparece en las colecciones: | (IBIS) Artículos (CBM) Artículos |
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MicroRNA_MO_2023_OA.pdf | 1,38 MB | Adobe PDF | Visualizar/Abrir |
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