RESUMO
The Hippo signaling pathway plays a crucial role in suppressing tumorigenesis. Physiologically, The Hippo signaling largely restricts its two downstream effectors, homologous oncoproteins Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), to a low level of activity by the MST1-SAV1 complex-induced kinase cascade. However, how the negative regulation induced by MST1-SAV1 complex is disrupted to exhibit constitutive YAP/TAZ activation in cancer remains unclear. Herein, we reported that miR-130b directly repressed MST1 and SAV1 expression in human glioblastoma cells. Overexpression of miR-130b induced hyperactivation of the YAP/TAZ and enhanced expression of the Hippo signaling downstream genes CTGF and the pluripotency associated markers, including CD133, SOX2, Nanog, MYC and BMI1, leading to promotion of glioblastoma stem cell phenotype. Conversely, inhibition of miR-130b attenuated these effects. These findings provide a novel mechanism for Hippo signaling inactivation in cancer, indicating not only a potentially pivotal role for miR-130b in the progression of glioblastoma, but also may represent a new therapeutic target.
Assuntos
Neoplasias Encefálicas/genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , MicroRNAs/genética , Células-Tronco Neoplásicas/metabolismo , Proteínas Serina-Treonina Quinases/genética , Aciltransferases , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Genes Reporter , Genótipo , Glioblastoma/metabolismo , Glioblastoma/patologia , Via de Sinalização Hippo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Luciferases/genética , Luciferases/metabolismo , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/patologia , Fenótipo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Cultura Primária de Células , Proteínas Serina-Treonina Quinases/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Sinalização YAPRESUMO
PURPOSE: To analyze the clinical manifestations, radiological features, and surgical outcomes in 30 pediatric intracranial hydatid cysts. METHODS: We reviewed the clinical, radiological, and surgical aspects of pediatric intracranial hydatid cysts patients who received surgical treatment at the Neurosurgical department of Xinjiang Medical University between the years 1985 to 2007, retrospectively. RESULTS: Headache and vomiting were the most common initial symptoms in our series. Neurological deficits from the mass effect of the cysts were seen in 15 cases, including hemiparesis, visual deficit, and diplopia. Epilepsy occurred only in one patient with temporal lobe hydatid cyst. On computed tomography (CT), it presented as a round-shaped and thin-walled homogeneous low-density cystic lesion without surrounding edema and enhancement. Only five patients had a magnetic resonance imaging (MRI) scan, and presented low signal intensity on T1-weighted image and high signal intensity on T2-weighted image. Surgical removal of cyst was performed in all cases and intact removal was done in 29 cases. However, one cyst ruptured during the dissection of cyst wall, thus, resulting in one death. There were no additional neurological deficits which were caused directly by surgery. CONCLUSION: Increased intracranial pressure is common in patients with cerebral hydatid disease. CT and MRI are the first-line diagnostic procedures. Surgery is the treatment of choice for the majority of intracranial hydatid cysts. Multiple and deep seated lesions should receive medical treatment postoperatively.
