miR-34c抑制脑胶质瘤生长的分子机制
摘要
业已表明miR-34c表达受p53的调控,并在肿瘤形成中起着重要的作用。本研究首次发现miR-34c在脑胶质瘤中呈显著下调的原因是该基因上游启动子区域甲基化而使其功能失活。同时我们也发现过表达miR-34c能抑制脑胶质瘤细胞生长和浸润,并使细胞周期发生G1期延滞。此外,我们还首次发现miR-34c能直接靶向调控Raf1,该基因在脑胶质瘤发生过程中发挥重要作用。概而言之,我们的研究结果提示miR-34c可能是脑胶质瘤的一个新的抑癌基因,并可能作为脑胶质瘤临床诊治的一个潜在的新靶点。
It has been shown mir-34c play an important role in tumorigenesis through modulating the p53 initiated gene expression and to serve as a tumor suppressor in various tumors. Here, we report that mir-34c is down-regulated in glioma and the DNA methylation state of 18 CpG inucleotides upstream of the miR-34c gene causes it down-regulation. Induction of miR-34c leads to Gl arrest and inhibits glioma growth and invasion. Moreover, Raf-1 has been identified as a novel target of mir-34c. Mir-34c transfection could repress the Raf-1 expression. Our data indicate that mir-34c might be a novel tumor suppressor in glioma and a potential therapeutic target in brain cancer therapy.
It has been shown mir-34c play an important role in tumorigenesis through modulating the p53 initiated gene expression and to serve as a tumor suppressor in various tumors. Here, we report that mir-34c is down-regulated in glioma and the DNA methylation state of 18 CpG inucleotides upstream of the miR-34c gene causes it down-regulation. Induction of miR-34c leads to Gl arrest and inhibits glioma growth and invasion. Moreover, Raf-1 has been identified as a novel target of mir-34c. Mir-34c transfection could repress the Raf-1 expression. Our data indicate that mir-34c might be a novel tumor suppressor in glioma and a potential therapeutic target in brain cancer therapy.
引文
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