Identification Of MiRNA-dependamt Regulatory Networks In Glioma

Since microRNAs (miRNAs) were identified in 1993, studies of these tine molecules became as a hot area in life sciences. It has been reported that miRNAs play an important roles in glioma. However, the complex miRNA-dependant regulatory networks in tumorgenesis remain uncoverd. In this study, several miRNAs which were deregulated in glioma were identified, and the miRNA-dependamt regulatory networks were revealed.PartⅠ. The expression, regulation and function of miR-29a in glioma. In this part of study, we demonstrated that miR-29a is down-regulated in glioma and serves as a tumor suppressor gene. miR-29a suppressed tumorigenesis in glioma through repressing MDM4, Bc1212 and CDK6, while the under-expression of miR-29a was transcriptionally regulated by p53. Moreover, quantitative real-time PCR analysis of tumor specimens indicate that mir-29a levels are inversely correlates with glioma malignancy. Thus, miR-29a might be a potential dianositic and therapeutic target in glioma.PartⅡ. The expression, regulation and function of miR-210 in glioma. In this study, we report miR-210 serves as an oncogene in glioma. Inhibition of miR-210 could repress cancer cell invasion. Importantly, miR-210 could be transcriptional activated by Spl and directly target cadherin-1. In addition, Spl is a direct target of miR-29a. Taken together, our data indicate that both mir-210 and mir-29a may play important roles in glioma invasion.PartⅢ. The expression, regulation and function of miR-34c in glioma. miR-34c is reported as a tumor suppressor in various tumors recently. However, its roles in glioma remain unknown. Here, we demonstrate that miR-34c inhibits glioma growth and invasion through repressing Raf-1 and that the silence of miR-34c expression in glioma is due to its promoter hypermethylation. In addition, quantitative real-time PCR analysis of tumor specimens indicate that miR-34c levels are inversely correlates with glioma malignancy. Thus, monitoring miR-34c expression in glioma and manipulation of its levels may provide new clues for glioma diagnosis and therapy.In summary, the aims of this study are to identify the disregulated miRNAs and to study their regulatory networks in glioma. Our data may provide new clues for the diagnosis and therapy in glioma.