miRNA array screening reveals cooperative MGMT-regulation between miR-181d-5p and miR-409-3p in glioblastoma.
miRNA array screening reveals cooperative MGMT-regulation between miR-181d-5p and miR-409-3p in glioblastoma.
复制标题
DOI：
10.18632/oncotarget.8618
复制
发表时间：
2016-05-10
期刊：
影响因子：
--
通讯作者：
Cabrini G
中科院分区：
文献类型：
--
作者：
Khalil S;Fabbri E;Santangelo A;Bezzerri V;Cantù C;Di Gennaro G;Finotti A;Ghimenton C;Eccher A;Dechecchi M;Scarpa A;Hirshman B;Chen C;Ferracin M;Negrini M;Gambari R;Cabrini G
O6-甲基鸟嘌呤-DNA 甲基转移酶 (MGMT) 的表达水平与预测胶质母细胞瘤患者对烷化化疗的反应相关。 MGMT启动子甲基化和已发表的MGMT调节microRNA（miRNA）并不能完全解释临床胶质母细胞瘤标本中MGMT的表达模式。在这里，我们使用基于全基因组微阵列的方法来识别 MGMT 调节 miRNA。除了之前鉴定的 miR-181d-5p 之外，我们的筛选还揭示了三种新型 MGMT 调节 miRNA：miR-127-3p、miR-409-3p 和 miR-124-3p。将这三种新型 miRNA 转染至 T98G 胶质母细胞瘤细胞系中可抑制 MGMT mRNA 和蛋白表达。然而，它们的 MGMT 抑制效果相对于 miR-181d-5p 转染的效果为 30-50%。对癌症基因组图谱 (TCGA) 和中国胶质瘤基因组图谱 (CGGA) 的计算机分析表明，miR-181d-5p 是唯一始终表现出与 MGMT mRNA 表达呈负相关的 miRNA。然而，相对于仅涉及任一 miRNA 的模型，纳入 miR-181d-5p 和 miR-409-3p 表达的统计模型可以更好地预测 MGMT 表达。我们的结果证实 miR-181d-5p 是调节 MGMT 的关键 miRNA。其他 MGMT 调节 miRNA，包括本报告中鉴定的 miR-409-3p，可以改变 miR-181d-5p 对 MGMT 表达的影响。因此，MGMT 表达是通过关键 MGMT 调节 miRNA 之间的相互作用来调节的。
The levels of expression of O6-methylguanine-DNA methyltransferase (MGMT) are relevant in predicting the response to the alkylating chemotherapy in patients affected by glioblastoma. MGMT promoter methylation and the published MGMT regulating microRNAs (miRNAs) do not completely explain the expression pattern of MGMT in clinical glioblastoma specimens. Here we used a genome-wide microarray-based approach to identify MGMT regulating miRNAs. Our screen unveiled three novel MGMT regulating miRNAs, miR-127-3p, miR-409-3p, and miR-124-3p, in addition to the previously identified miR-181d-5p. Transfection of these three novel miRNAs into the T98G glioblastoma cell line suppressed MGMT mRNA and protein expression. However, their MGMT- suppressive effects are 30–50% relative that seen with miR-181d-5p transfection. In silico analyses of The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) revealed that miR-181d-5p is the only miRNA that consistently exhibited inverse correlation with MGMT mRNA expression. However, statistical models incorporating both miR-181d-5p and miR-409-3p expression better predict MGMT expression relative to models involving either miRNA alone. Our results confirmed miR-181d-5p as the key MGMT-regulating miRNA. Other MGMT regulating miRNAs, including the miR-409-3p identified in this report, modify the effect of miR-181d-5p on MGMT expression. MGMT expression is, thus, regulated by cooperative interaction between key MGMT-regulating miRNAs.
登录
查看更多内容
影响因子：
3.7
作者：
Quintavalle C;Mangani D;Roscigno G;Romano G;Diaz-Lagares A;Iaboni M;Donnarumma E;Fiore D;De Marinis P;Soini Y;Esteller M;Condorelli G
通讯作者：
Condorelli G
影响因子：
3
作者：
Belanich, M;Randall, T;Yarosh, DB
通讯作者：
Yarosh, DB
影响因子：
8
作者：
Josson, S.;Gururajan, M.;Chung, L. W. K.
通讯作者：
Chung, L. W. K.
影响因子：
15.9
作者：
Godlewski, Jakub;Krichevsky, Anna M.;Bronisz, Agnieszka
通讯作者：
Bronisz, Agnieszka
影响因子：
9.7
作者：
Weng, Chunhua;Dong, Haojie;Xu, Zhengping
通讯作者：
Xu, Zhengping