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Título
Epigenetically regulated chromosome 14q32 miRNA cluster induces metastasis and predicts poor prognosis in lung adenocarcinoma patients
Autor
Año del Documento
2018
Editorial
American Association for Cancer Research
Descripción
Producción Científica
Documento Fuente
Molecular Cancer Research, 2018, vol. 16, n. 3, p. 390-402
Resumen
Most lung cancer deaths are related to metastases, which indicates the necessity of detecting and inhibiting tumor cell dissemination. Here, we aimed to identify miRNAs involved in metastasis of lung adenocarcinoma as prognostic biomarkers and therapeutic targets. To that end, lymph node metastasis–
associated miRNAs were identified in The Cancer Genome Atlas lung adenocarcinoma patient cohort (sequencing data; n ¼ 449) and subsequently validated by qRT-PCR in an independent
clinical cohort (n ¼ 108). Overexpression of miRNAs located
on chromosome 14q32 was associated with metastasis in lung
adenocarcinoma patients. Importantly, Kaplan–Meier analysis
and log-rank test revealed that higher expression levels of
individual 14q32 miRNAs (mir-539, mir-323b, and mir487a) associated with worse disease-free survival of never-smoker patients. Epigenetic analysis including DNA methylation
microarray data and bisulfite sequencing validation demonstrated that the induction of 14q32 cluster correlated with genomic
hypomethylation of the 14q32 locus. CRISPR activation technology, applied for the first time to functionally study the
increase of clustered miRNA levels in a coordinated manner,
showed that simultaneous overexpression of 14q32 miRNAs
promoted tumor cell migratory and invasive properties. Analysis
of individual miRNAs by mimic transfection further illustrated
that miR-323b-3p, miR-487a-3p, and miR-539-5p significantly
contributed to the invasive phenotype through the indirect
regulation of different target genes. In conclusion, overexpression of 14q32 miRNAs, associated with the respective genomic
hypomethylation, promotes metastasis and correlates with poor
patient prognosis in lung adenocarcinoma
Materias Unesco
3207.13 Oncología
Palabras Clave
Cáncer
miARN
ISSN
1541-7786
Revisión por pares
SI
Version del Editor
Propietario de los Derechos
© American Association for Cancer Research
Idioma
eng
Tipo de versión
info:eu-repo/semantics/publishedVersion
Derechos
openAccess
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