The miR-183∼96∼182 cluster promotes tumorigenesis in a mouse model of medulloblastoma.
The miR-183∼96∼182 cluster promotes tumorigenesis in a mouse model of medulloblastoma.
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DOI：
10.7555/jbr.27.20130010
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发表时间：
2013-11
影响因子：
2.3
通讯作者：
Cheng SY
中科院分区：
文献类型：
--
作者：
Zhang Z;Li S;Cheng SY
髓母细胞瘤是小儿最常见的恶性脑肿瘤。一些被认为起源于小脑颗粒神经元祖细胞（CGNP），其不能经历正常的细胞周期退出和分化。microRNA对髓母细胞瘤的发生和发展的作用仍然知之甚少。在几个侵袭性亚组中已经注意到miR-183、miR-96、miR-182 microRNA簇的表达增加。我们发现，在激活的音刺猬（Shh）信号通路的背景下，Pten基因缺失的髓母细胞瘤中miR-183、96、182的表达更高。CGNP中的异位miR-183、96、182表达与外源性Shh协同增加增殖，其作用依赖于hedgehog信号传导激活。我们的研究结果表明，一个新的microRNA簇，miR-183 <$96 <$182，在功能上与小鼠髓母细胞瘤的发展中的Shh信号通路合作。
Medulloblastoma is the most common malignant pediatric brain tumor. Some are thought to originate from cerebellar granule neuron progenitors (CGNPs) that fail to undergo normal cell cycle exit and differentiation. The contribution of microRNAs to the initiation and progression of medulloblastoma remains poorly understood. Increased expression of the miR-183∼96∼182 cluster of microRNAs has been noted in several aggressive subgroups. We identified that expression of miR-183∼96∼182 was higher in medulloblastomas with Pten gene loss in the background of the activated sonic hedgehog (Shh) signaling pathway. Ectopic miR-183∼96∼182 expression in CGNPs synergized with exogenous Shh to increase proliferation and its role depended on hedgehog signaling activation. Our findings suggest a new microRNA cluster, the miR-183∼96∼182, functionally collaborates with the Shh signaling pathway in the development of medulloblastomas in mice.