Abstract
BackgroundMiR-92b was upregulated in gliomas. However, the association of miR-92b with glioma cell apoptosis and survival remains unknown.MethodsProliferation capability of glioma cells upon tranfection with miR-92b mimics or inhibitors was detected by mutiple analyses, including MTT assays, colony formation assay. Apoptosis abilities of glioma cells were detected by flow cytometric analysis. The target of miR-92b was determined by luciferase reporter and western blot. The association of miR-92b with outcome was examined in twenty glioma patients.ResultsMiR-92b expression was significantly increased in high-grade gliomas compared with low-grade gliomas, and positively correlated with the degree of glioma infiltration. Over-expression of miR-92b increased cell proliferation, whereas knockdown of miR-92b decreased cell proliferation via modulating the levels of the target, Target prediction analysis and a dual luciferase reporting assay confirmed that the inhibitory protein-coding Dickkopf-3 gene (DKK3) was a direct target of miR-92b. Furthermore, miR-92b could regulate the expression of downstream genes of the Wnt/beta-catenin signaling pathway, such as Bcl2, c-myc and p-c-Jun, in glioma cells. Finally, the increased level of miR-92b expression in high-grade gliomas confers poorer overall survival.ConclusionsThe present data indicates that miR-92b directly regulate cell proliferation and apoptosis by targeting DKK3 and act as prognostic factors for glioma patients.
Highlights
A glioma is the most common form of neural malignancy
Expression and clinical significance of miR-92b in gliomas To identify the miRNAs that are potentially involved in gliomas, we first examined the miRNA expression profiles in 8 glioma tissues and their corresponding nontumorous tissues using Agilent Human miRNA array (v.12.0), which consists of 873 capture probes for mature human miRNAs
After the microRNA expression was normalized by U6 expression, The microarray results showed that 20 miRNAs were significantly overexpressed in the glioma tissues (T) compared with their corresponding normal tissues (N)
Summary
A glioma is the most common form of neural malignancy. High grade glioma, especially glioblastoma, is a leading cause of brain cancer fatality involving highly invasive and neoplastic growth. Increasing evidence suggests that the progression of a glioma is relative to the rate of both cell proliferation and apoptosis. Understanding the main regulatory mechanism of gliomas is key to the development of effective therapeutic approaches against this malignancy. The deregulation of miRNAs has been observed in various types of human malignancies, including lymphoma, colorectal cancer, lung cancer, breast cancer, papillary thyroid carcinoma, hepatocellular carcinoma and glioblastoma [10,11,12,13]. A few studies suggest that the downregulation of miRNAs may play a critical role in cancer progression by affecting proliferation and apoptosis [18,19,20]. Mir-92b was reported to modulate the expression of the inhibitory protein-coding Dickkopf-3 gene (DKK3)[22]. The association of miR-92b with glioma cell apoptosis and survival remains unknown
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