MicroRNA-26a Promotes Tumor Growth and Angiogenesis in Glioma by Directly Targeting Prohibitin
MicroRNA-26a Promotes Tumor Growth and Angiogenesis in Glioma by Directly Targeting Prohibitin
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DOI：
10.1111/cns.12149
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发表时间：
2013-10-01
影响因子：
5.5
通讯作者：
Jiang, Bing-Hua
中科院分区：
文献类型：
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作者：
Qian, Xu;Zhao, Peng;Jiang, Bing-Hua
背景与目的胶质瘤是成人原发性恶性脑肿瘤的主要类型.已经在胶质瘤中观察到microRNA-26 a（miR-26 a）的上调。然而，miR-26 a在胶质瘤中的生物学功能和分子机制仍有待阐明。通过生物信息学搜索和分子生物学分析，确定了miR-26 a的新靶点。胶质瘤标本和正常脑组织中的miR-26 a的表达水平和其target.ResultsForced表达的miR-26 a在胶质瘤细胞显着增加生长速度和集落形成在体外和肿瘤生长和血管生成在体内，而减少miR-26 a的表达发挥相反的作用。MiR-26 a直接靶向在胶质瘤标本中表达水平下调的抑制素（PHB）。结论miR-26 a在体外和体内均能调控PHB并促进胶质瘤的进展，miR-26 a及其靶基因PHB与胶质瘤的发生发展相关，为今后开展基于microRNA的胶质瘤治疗提供了理论依据。
Backgrounds and AimsGlioma accounts for the majority of primary malignant brain tumors in adults. Upregulation of microRNA-26a (miR-26a) has been observed in glioma. However, the biological function and molecular mechanism of miR-26a in glioma remain to be elucidated.MethodsGlioma cells stably overexpressing or down-expressing miR-26a were analyzed for both in vitro and in vivo biological functions. Novel target of miR-26a was identified by bioinformatics searching and molecular biological assays. Glioma specimens and normal brain tissues were analyzed for both expression levels of miR-26a and its target.ResultsForced expression of miR-26a in glioma cells significantly increased both growth rate and colony formation in vitro and tumor growth and angiogenesis in vivo, while reduced expression of miR-26a played opposite roles. MiR-26a directly targeted prohibitin (PHB) whose expression levels were downregulated in glioma specimens. The levels of miR-26a were inversely correlated with PHB expression levels in glioma samples and strongly correlated with clinical WHO grades of glioma.ConclusionThese results reveal that miR-26a regulates PHB and promotes glioma progression both in vitro and in vivo and that miR-26a and its target PHB are associated with glioma development, which can be helpful in developing microRNA-based treatment for glioma in the future.