RESUMO
Glioma invasion is a main cause of a poor prognosis and relapse in patients suffering from the disease. However, the molecular mechanisms responsible for glioma cell invasion remain poorly understood. In this study, the characteristics of exosomes were identified using electron microscope (TEM), and western blot analysis. The potential mechanism of long noncoding RNA (lncRNA) activated by TGFß (lncRNAATB) was demonstrated using luciferase reporter assays and RNA immunoprecipitation. We found that glioma cellderived exosomes promoted the activation of astrocytes and had the ability to shuttle long noncoding RNA (lncRNA) activated by TGFß (lncRNAATB) to astrocytes. More importantly, lncRNAATB activated astrocytes through the suppression of microRNA (miRNA or miR)2043p in an Argonaute 2 (Ago2)dependent manner. Furthermore, astrocytes activated by lncRNAATB in turn promoted the migration and invasion of glioma cells. Taken together, the findings of this study suggest that lncRNAATB may play an important role in modulating glioma microenvironment through exosomes. Thus, a better understanding of this process may provide implications for the prevention of highly invasive glioma.
Assuntos
Exossomos/genética , Glioma/genética , RNA Longo não Codificante/genética , Fator de Crescimento Transformador beta/genética , Astrócitos/metabolismo , Astrócitos/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Humanos , MicroRNAs/genética , Microscopia Eletrônica , Invasividade Neoplásica/genética , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Microambiente Tumoral/genéticaRESUMO
Malignant glioma is one of the most common primary human tumors in the central nervous system. The molecular mechanisms of the progression and development of glioma have been largely unexplored. In this study, we illustrated that the expression of Dok7 was downregulation in human glioma tissues. Dok7 overexpression significantly inhibits proliferation and colony formation in vitro, and the xenograft tumor formation in vivo. In addition, 5-Aza-2'-deoxycytidine (5-Aza), a DNA methylation inhibitor, preventing the loss of Dok7 expression by decreasing aberrant hypermethylation of Dok7 promoter in glioma cells. More importantly, DNMT1 knockdown induced the demethylation of Dok7 promoter, and enhanced the expression of Dok7 in gliomas. These results suggest that epigenetic silencing of Dok7 may provide a novel glioma treatment strategy.
