Expression of miR-124 inhibits growth of medulloblastoma cells
Expression of miR-124 inhibits growth of medulloblastoma cells
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DOI：
10.1093/neuonc/nos281
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发表时间：
2013-01-01
期刊：
影响因子：
15.9
通讯作者：
Gupta, Nalin
中科院分区：
文献类型：
--
作者：
Silber, Joachim;Hashizume, Rintaro;Gupta, Nalin
髓母细胞瘤是儿童中最常见的恶性脑肿瘤，并且相当数量的患者由于肿瘤进展而死亡。CDK 6的过表达存在于大约三分之一的髓母细胞瘤中，并且是这种疾病的独立预后不良标志物。MicroRNA（miR）-124抑制CDK 6的表达并防止胶质母细胞瘤和髓母细胞瘤细胞的体外增殖。我们在体外和体内检测了miR-124过表达对髓母细胞瘤细胞的影响，并比较了具有低和高CDK 6表达的细胞系。miR-124过表达抑制髓母细胞瘤细胞的增殖，并且这种作用主要通过miR-124对CDK 6的作用介导。我们进一步表明，诱导表达的miR-124有效地抑制啮齿类动物髓母细胞瘤异种移植肿瘤的生长。对miR-124的进一步测试将有助于确定髓母细胞瘤临床前模型结合各种治疗策略的最终治疗潜力。
Medulloblastoma is the most common malignant brain tumor in children, and a substantial number of patients die as a result of tumor progression. Overexpression of CDK6 is present in approximately one-third of medulloblastomas and is an independent poor prognostic marker for this disease. MicroRNA (miR)-124 inhibits expression of CDK6 and prevents proliferation of glioblastoma and medulloblastoma cells in vitro. We examined the effects of miR-124 overexpression on medulloblastoma cells both in vitro and in vivo and compared cell lines that have low and high CDK6 expression. MiR-124 overexpression inhibits the proliferation of medulloblastoma cells, and this effect is mediated mostly through the action of miR-124 upon CDK6. We further show that induced expression of miR-124 potently inhibits growth of medulloblastoma xenograft tumors in rodents. Further testing of miR-124 will help define the ultimate therapeutic potential of preclinical models of medulloblastoma in conjunction with various delivery strategies for treatment.