Downregulation of 14q32 microRNAs in Primary Human Desmoplastic Medulloblastoma.
Downregulation of 14q32 microRNAs in Primary Human Desmoplastic Medulloblastoma.
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DOI：
10.3389/fonc.2013.00254
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发表时间：
2013
影响因子：
4.7
通讯作者：
Yunes JA
中科院分区：
文献类型：
--
作者：
Lucon DR;Rocha Cde S;Craveiro RB;Dilloo D;Cardinalli IA;Cavalcanti DP;Aguiar Sdos S;Maurer-Morelli C;Yunes JA
髓母细胞瘤（MB）是最常见的儿科癌症之一，可能起源于小脑祖神经元的异常发育。microRNA（miRNA）在中枢神经系统发育中起重要作用。微阵列分析用于研究在年轻时（1或2岁）诊断的促纤维增生性MB患者中的miRNA表达。正常胎儿或新生儿小脑作为对照。共发现84个差异表达的miRNAs（64个下调，20个上调），其中32个（32/64）属于14 q32位点的miRNAs簇，提示该miRNAs位点在MB中作为一个模块受到调控。通过分析公开的基因表达数据集，研究了14 q32 miRNA下调的可能机制。首先，雌激素相关受体-γ（ESRRG）的表达，一些14 q32 miRNA的正性转录调节因子，被发现在促结缔组织增生MB下调。其次，与正常小脑相比，MB中父母印记基因MEG 3的表达较低，表明14 q32位点可能存在表观遗传沉默。选择miR-129- 5 p（11p11.2/7q32.1）、miR-206（6p12.2）和miR-323- 3 p（14q32.2）用于DAOY细胞中的功能研究。使用模拟物过表达miR-129- 5 p降低DAOY增殖。未发现miR-206或miR-323模拟物的作用。
Medulloblastoma (MB) is one of the most common pediatric cancers, likely originating from abnormal development of cerebellar progenitor neurons. MicroRNA (miRNA) has been shown to play an important role in the development of the central nervous system. Microarray analysis was used to investigate miRNA expression in desmoplastic MB from patients diagnosed at a young age (1 or 2 years old). Normal fetal or newborn cerebellum was used as control. A total of 84 differentially expressed miRNAs (64 downregulated and 20 upregulated) were found. Most downregulated miRNAs (32/64) were found to belong to the cluster of miRNAs at the 14q32 locus, suggesting that this miRNA locus is regulated as a module in MB. Possible mechanisms of 14q32 miRNAs downregulation were investigated by the analysis of publicly available gene expression data sets. First, expression of estrogen-related receptor-γ (ESRRG), a reported positive transcriptional regulator of some 14q32 miRNAs, was found downregulated in desmoplastic MB. Second, expression of the parentally imprinted gene MEG3 was lower in MB in comparison to normal cerebellum, suggesting a possible epigenetic silencing of the 14q32 locus. miR-129-5p (11p11.2/7q32.1), miR-206 (6p12.2), and miR-323-3p (14q32.2), were chosen for functional studies in DAOY cells. Overexpression of miR-129-5p using mimics decreased DAOY proliferation. No effect was found with miR-206 or miR-323 mimics.