MicroRNA-31 suppresses medulloblastoma cell growth by inhibiting DNA replication through minichromosome maintenance 2.
MicroRNA-31 suppresses medulloblastoma cell growth by inhibiting DNA replication through minichromosome maintenance 2.
复制标题
MicroRNA-31 通过微小染色体维持 2 抑制 DNA 复制，从而抑制髓母细胞瘤细胞生长。
DOI：
10.18632/oncotarget.2043
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发表时间：
2014-07-15
期刊：
影响因子：
--
通讯作者：
Cheng SY
中科院分区：
文献类型：
--
作者：
Jin Y;Xiong A;Zhang Z;Li S;Huang H;Yu TT;Cao X;Cheng SY
髓母细胞瘤是一种侵袭性儿童脑肿瘤，预后差。近年来的研究表明，microRNA表达的异常在肿瘤发生中起重要作用。通过比较小鼠髓母细胞瘤和正常小脑组织中microRNA的水平，我们鉴定了一组下调的microRNA，包括miR-31。在这里，我们发现，在许多实体瘤细胞系中，9p21.3处围绕人miR-31的基因组区域经常缺失，并且将miR-31重新引入DAOY细胞（一种缺乏miR-31的人髓母细胞瘤细胞系）中，强烈抑制细胞生长，导致细胞周期停滞在G1/S边界，并抑制体外集落形成和裸鼠异种移植瘤发生。小鼠髓母细胞瘤的全局基因表达谱和microRNA靶标的生物信息学分析表明，微小染色体维持复合物组分2（MCM 2）可能是miR-31抑制细胞生长的靶基因。我们证明了miR-31通过其3 '非翻译区抑制MCM 2表达，在DAOY细胞中MCM 2的敲低导致与miR-31恢复相当的生长抑制程度，并且miR-31的过表达减少了G1/S转换点处的MCM 2的染色质负载。综上所述，这些数据表明miR-31通过MCM 2负调控DNA复制来抑制髓母细胞瘤肿瘤发生。
Medulloblastoma is an aggressive childhood brain tumor with poor prognosis. Recent studies indicate that dys-regulation of microRNA expression plays important roles in tumorigenesis. By comparing microRNA levels between mouse medulloblastoma and normal cerebellar tissues, we identified a set of down-regulated microRNAs including miR-31. Here, we show that the genomic region surrounding human miR-31 at 9p21.3 is frequently deleted in many solid tumor cell lines, and reintroducing miR-31 into DAOY cells, a line of human medulloblastoma cells devoid of miR-31, strongly suppresses cell growth, causes cell cycle arrest at the G1/S boundary, and inhibits colony formation in vitro and xenograft tumorigenesis in nude mice. Global gene expression profiling of mouse medulloblastomas and bioinformatics analyses of microRNA targets suggest that minichromosome maintenance complex component 2 (MCM2) is a likely target gene of miR-31 in suppressing cell growth. We demonstrate that miR-31 inhibits MCM2 expression via its 3'-untranslated region, that knockdown of MCM2 in DAOY cells leads to a degree of growth inhibition comparable to that by miR-31 restoration, and that overexpression of miR-31 reduces the chromatin loading of MCM2 at the point of G1/S transition. Taken together, these data indicate that miR-31 suppresses medulloblastoma tumorigenesis by negatively regulating DNA replication via MCM2.
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影响因子：
11.2
作者：
Lin PC;Chiu YL;Banerjee S;Park K;Mosquera JM;Giannopoulou E;Alves P;Tewari AK;Gerstein MB;Beltran H;Melnick AM;Elemento O;Demichelis F;Rubin MA
通讯作者：
Rubin MA
影响因子：
37.3
作者：
Augoff K;McCue B;Plow EF;Sossey-Alaoui K
通讯作者：
Sossey-Alaoui K
影响因子：
15.9
作者：
Dolecek, Therese A.;Propp, Jennifer M.;Kruchko, Carol
通讯作者：
Kruchko, Carol
DOI：
10.1073/pnas.94.11.5611
发表时间：
1997-05-27
影响因子：
11.1
作者：
Donovan, S;Harwood, J;Diffley, JFX
通讯作者：
Diffley, JFX
影响因子：
10.5
作者：
Ge, Xin Quan;Jackson, Dean A;Blow, J Julian
通讯作者：
Blow, J Julian