RESUMEN
Glioma stem cells (GSCs) are thought to be critical for resistance to radiotherapy and chemotherapy and for tumor recurrence after surgery in glioma patients. Identification of new therapeutic strategies that can target GSCs may thus be critical for improving patient survival. MicroRNAs (miRNAs) are small non-coding RNAs that function as tumor suppressors or oncogenes. In this study, we confirmed that miR-107 was down-regulated in GSCs. To investigate the role of miR-107 in tumorigenesis of GSCs, a lentiviral vector over-expressing miR-107 in U87GSCs was constructed. We found that over-expression of miR-107 suppressed proliferation and down-regulated Notch2 protein and stem cell marker (CD133 and Nestin) expression in U87GSCs. Furthermore, enhanced miR-107 expression significantly inhibited U87GSC invasion and reduced matrix metalloproteinase-12 expression. miR-107 also suppressed U87GSCs xenograft growth in vivo. These findings suggest that miR-107 is involved in U87GSCs growth and invasion and may provide a potential therapeutic target for glioma treatment.
Asunto(s)
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Glioma/genética , Glioma/patología , MicroARNs/metabolismo , Células Madre Neoplásicas/patología , Antígeno AC133 , Animales , Antígenos CD/metabolismo , Secuencia de Bases , Neoplasias Encefálicas/enzimología , Línea Celular Tumoral , Proliferación Celular , Regulación hacia Abajo/genética , Regulación Neoplásica de la Expresión Génica , Glioma/enzimología , Glicoproteínas/metabolismo , Humanos , Lentivirus/metabolismo , Metaloproteinasa 12 de la Matriz/metabolismo , Ratones , Ratones Desnudos , MicroARNs/genética , Datos de Secuencia Molecular , Invasividad Neoplásica , Células Madre Neoplásicas/enzimología , Nestina/genética , Nestina/metabolismo , Péptidos/metabolismo , Receptor Notch2/genética , Receptor Notch2/metabolismo , Transducción Genética , Regulación hacia Arriba/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Spinal cord injury (SCI) can result in irreversible motor and sensory deficits. However, up to data, clinical first-line drugs have ambiguous benefits and debilitating side effects, mainly due to the insufficient accumulation, poor physiological barrier penetration, and lack of spatio-temporal controlled release at lesion tissue. Herein, we proposed a supramolecular assemblies composed of hyperbranched polymer-formed core/shell structure through host-guest interactions. Such HPAA-BM@CD-HPG-C assemblies co-loaded with p38 inhibitor (SB203580) and insulin-like growth factor 1(IGF-1) are able to achieve time- and space-programmed sequential delivery benefiting from their cascaded responsiveness. The core-shell disassembly of HPAA-BM@CD-HPG-C occurs in acidic micro-environment around lesion, achieving preferentially the burst release of IGF-1 to protect survival neurons. Subsequently, the HPAA-BM cores containing SB203580 are endocytosed by the recruited macrophages and degraded by intracellular GSH, accelerating the release of SB203580 to promote the conversion from M1 to M2 macrophage. Hence, the successive synergy of neuroprotection and immunoregulation effects contribute to subsequent nerve repair and locomotor recovery as demonstrated in vitro and in vivo studies. Thus, our fabrication provides a strategy that multiple drugs co-delivery in a spatio-temporal selective manner adapting to the disease progression through self-cascaded disintegration, are expected to realize multidimensional precise treatment of SCI.