| Glioma is a type of tumor that starts in the brain or spine and arises from glial cells. Glioma makes up approximately30%of all tumors from brain and central nervous system, and80%of all malignant brain tumors, and accounts for the majority of primary malignant brain tumors in adults. High-grade gliomas are highly-vascular tumors and have a tendency to infiltrate into other tissues. On the other hand, low-grade gliomas grow slowly, often over many years, and can be followed without treatment unless they grow and cause symptoms. Treatment for gliomas depends on the location, the cell type and the grade of malignancy. Often, the major therapeutic method is surgery, as well as radiation therapy and chemotherapy. Because of the characteristics of highly invasion rate and high levels of angiogenesis, it is impossible to completely remove all lesions with surgery, the radiotherapy and chemotherapy curative effects are not ideal, therefore, glioma is still one of the worst prognosis of systemic tumors. Thus, it is important to study the pathogenesis mechanism to seek new methods of diagnosis and treatment of glioma.MicroRNA (miRNA) is a small non-coding RNA molecule found in plants and animals, which functions in transcriptional and post-transcriptional regulation of gene expression. The human genome may encode more than1000different kinds of miRNAs, which may target about60%of mammalian genes and are abundant in many human cell types. MiRNAs regulate physiological and pathological process, such as cell growth, cell cycle and apoptosis. Aberrant expression levels of miRNAs have been implicated in numerous diseases, including many cancers. MiRNAs may function as oncogenes or tumor suppressors, and miRNA-based therapies are obtained more and more attentions.We analyzed the expression levels of miR-26a in nine normal brain tissues, ten glioma tissues at Grades Ⅱ/Ⅲ and seventeen glioma tissues at Grades Ⅲ/Ⅳ, and up-regulation levels of microRNA-26a (miR-26a) have been observed in glioma tissues. To determine the role of miR-26a in glioma progression, we studied the biological functions of miR-26a in glioma cells and the correlation between miR-26a expression profile and clinical grades of glioma. We found that forced expression of miR-26a in glioma cells significantly increased both growth rate and anchorage-independent colony formation in vitro, and tumor growth and angiogenesis in vivo, while reduced expression levels of miR-26a played opposite roles in tumors cells both in vitro and in vivo. MiR-26a directly targeted prohibitin (PHB) whose expression levels were down-regulated in glioma specimens when compared to normal brain tissues. The levels of miR-26a were inversely correlated with PHB expression levels in glioma samples, and strongly correlated with clinical WHO grades of glioma.In summary, miR-26a promotes tumor growth and angiogenesis by targeting PHB and regulating the downstream signaling molecules; miR-26a promotes glioma progression both in vitro and in vivo. Levels of miR-26a are associated with glioma development with inverse correlation with its target PHB, which may be useful in developing microRNA-based drugs for treating glioma in the future. |
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