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Oncotarget ; 6(29): 26971-81, 2015 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-26284486

RESUMO

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.


Assuntos
Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/líquido cefalorraquidiano , Exossomos/metabolismo , Glioma/sangue , Glioma/líquido cefalorraquidiano , MicroRNAs/metabolismo , Adulto , Idoso , Proteínas Reguladoras de Apoptose/metabolismo , Astrocitoma/sangue , Astrocitoma/líquido cefalorraquidiano , Astrocitoma/diagnóstico , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/diagnóstico , Linhagem Celular Tumoral , Progressão da Doença , Ependimoma/sangue , Ependimoma/líquido cefalorraquidiano , Ependimoma/diagnóstico , Feminino , Proteínas Ligadas por GPI/metabolismo , Regulação Neoplásica da Expressão Gênica , Glioblastoma/sangue , Glioblastoma/líquido cefalorraquidiano , Glioblastoma/diagnóstico , Glioma/diagnóstico , Humanos , Estimativa de Kaplan-Meier , Lentivirus/genética , Masculino , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , PTEN Fosfo-Hidrolase/metabolismo , Prognóstico , Proteínas de Ligação a RNA/metabolismo , Curva ROC , Recidiva , Fatores de Tempo
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