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Oncotarget ; 6(29): 26971-81, 2015 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-26284486

RESUMEN

Glioma is a most common type of primary brain tumors. Extracellular vesicles, in the form of exosomes, are known to mediate cell-cell communication by transporting cell-derived proteins and nucleic acids, including various microRNAs (miRNAs). Here we examined the cerebrospinal fluid (CSF) from patients with recurrent glioma for the levels of cancer-related miRNAs, and evaluated the values for prognosis by comparing the measures of CSF-, serum-, and exosome-contained miR-21 levels. Samples from seventy glioma patients following surgery were compared with those from brain trauma patients as a non-tumor control group. Exosomal miR-21 levels in the CSF of glioma patients were found significantly higher than in the controls; whereas no difference was detected in serum-derived exosomal miR-21 expression. The CSF-derived exosomal miR-21 levels correlated with tumor spinal/ventricle metastasis and the recurrence with anatomical site preference. From additional 198 glioma tissue samples, we verified that miR-21 levels associated with tumor grade of diagnosis and negatively correlated with the median values of patient overall survival time. We further used a lentiviral inhibitor to suppress miR-21 expression in U251 cells. The results showed that the levels of miR-21 target genes of PTEN, RECK and PDCD4 were up-regulated at protein levels. Therefore, we concluded that the exosomal miR-21 levels could be demonstrated as a promising indicator for glioma diagnosis and prognosis, particularly with values to predict tumor recurrence or metastasis.


Asunto(s)
Neoplasias Encefálicas/sangre , Neoplasias Encefálicas/líquido cefalorraquídeo , Exosomas/metabolismo , Glioma/sangre , Glioma/líquido cefalorraquídeo , MicroARNs/metabolismo , Adulto , Anciano , Proteínas Reguladoras de la Apoptosis/metabolismo , Astrocitoma/sangre , Astrocitoma/líquido cefalorraquídeo , Astrocitoma/diagnóstico , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/diagnóstico , Línea Celular Tumoral , Progresión de la Enfermedad , Ependimoma/sangre , Ependimoma/líquido cefalorraquídeo , Ependimoma/diagnóstico , Femenino , Proteínas Ligadas a GPI/metabolismo , Regulación Neoplásica de la Expresión Génica , Glioblastoma/sangre , Glioblastoma/líquido cefalorraquídeo , Glioblastoma/diagnóstico , Glioma/diagnóstico , Humanos , Estimación de Kaplan-Meier , Lentivirus/genética , Masculino , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Fosfohidrolasa PTEN/metabolismo , Pronóstico , Proteínas de Unión al ARN/metabolismo , Curva ROC , Recurrencia , Factores de Tiempo
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