RESUMEN

Gliomas are highly malignant tumors, the most common of which are astrocytomas. A growing number of studies suggest that dysregulation of miRNAs is a frequent event contributing to the pathogenesis of gliomas. In this study, we found that over-expression of miR-132 inhibited cell proliferation and migration and triggered apoptosis, while knockdown of miR-132 showed opposite effects. PEA-15 was identified as a direct target of miR-132. Reintroduction of PEA-15 without 3'UTR region reversed the inhibitory effects of miR-132 on cell proliferation, migration, and apoptosis. MiR-132 was inversely correlated with the PEA-15 expression. CREB (cAMP response element binding protein) and KLF (Krüppel-like factor 8) were conformed as transcription factors of miR-132, which bidirectionally regulate the expression of miR-132. Our study suggests that miR-132 is an important tumor suppressor of astrocytoma progression by targeting PEA-15, while CREB and KLF can modulate the expression of miR-132, thus providing new insight into the molecular mechanisms underlying astrocytoma progression in vitro.

Asunto(s)

Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Regulación Neoplásica de la Expresión Génica/fisiología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , MicroARNs/metabolismo , Fosfoproteínas/metabolismo , Análisis de Varianza , Apoptosis/genética , Apoptosis/fisiología , Proteínas Reguladoras de la Apoptosis , Astrocitoma/patología , Neoplasias Encefálicas/patología , Proteína de Unión a CREB/genética , Proteína de Unión a CREB/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Movimiento Celular/fisiología , Proliferación Celular/genética , Proliferación Celular/fisiología , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica/genética , Glioma , Células HEK293 , Humanos , Factores de Transcripción de Tipo Kruppel , MicroARNs/genética , ARN Mensajero , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Sincalida/metabolismo , Factores de Tiempo , Transfección