RESUMO
MicroRNAs (miRNAs) play a vital role in tumour biological and pathologic processes. In the present study, we aimed to detect the expression and biological role of miR-216b in glioma. Our data showed that miR-216b was significantly downregulated in human glioma tissues and cells. Ectopic expression of miR-216b inhibited the proliferation and invasion of U87 and U251 cells and suppressed the growth of xenograft tumours in vivo. Bioinformatic and luciferase reporter analyses identified Forkhead box protein M1 (FoxM1) as a direct target of miR-216b. Overexpression of miR-216b inhibited the expression of FoxM1 in glioma cells. Rescue experiments demonstrated that co-transfection of FoxM1 lacking the 3'-untranslated region partially prevented miR216b-induced inhibition of glioma cell growth and invasion. In vivo studies indicated that ectopic expression of miR-216b impeded the proliferation of glioma xenograft tumours in nude mice, coupled with a decreased in FoxM1 protein expression and the percentage of Ki-67-positive tumour cells. Taken together, our results provide evidence of the suppressive activity of miR216b in glioma, which is largely ascribed to downregulation of FoxM1. Restoration of miR-216b may provide a novel potential therapeutic agent for glioma.
Assuntos
Movimento Celular/genética , Proteína Forkhead Box M1/genética , Glioma/genética , MicroRNAs/genética , Invasividade Neoplásica/genética , Regiões 3' não Traduzidas/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Glioma/patologia , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Transfecção/métodosRESUMO
OBJECTIVE: To explore the molecular mechanism of microRNA-599(miR-599) in the migration and invasion of glioma. RESULT: Clinicopathological characteristics of 33 patients were analyzed. Based on reverse transcription-PCR, miR-599 was down-regulated in glioma tissues compared with adjacent normal brain tissues (P < 0.001). Moreover, negative correlations between miR-599 and periostin protein expression in glioma tissues (P < 0.01) and necrosis by magnetic resonance imaging (P < 0.05) were observed. Transwell and wound healing assays showed that overexpression of miR-599 inhibited glioma cell migration and invasion. miR-599 down-regulated periostin expression by targeting the 3'-untranslated region. Additionally, re-expression of periostin partial reversed the suppressive effect of miR-599 on migration and invasion in vitro and in vivo. CONCLUSION: microRNA-599 inhibits proliferation and invasion by down-regulating periostin expression in vitro and in vivo.
