The effects of MicroRNA transfections on global patterns of gene expression in ovarian cancer cells are functionally coordinated.
The effects of MicroRNA transfections on global patterns of gene expression in ovarian cancer cells are functionally coordinated.
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DOI：
10.1186/1755-8794-5-33
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发表时间：
2012-08-01
影响因子：
2.7
通讯作者：
McDonald JF
中科院分区：
文献类型：
--
作者：
Shahab SW;Matyunina LV;Hill CG;Wang L;Mezencev R;Walker LD;McDonald JF
MicroRNAs(MiRNAs)是一类与包括癌症在内的许多疾病有关的小RNA。MiRNAs在卵巢癌和其他癌症的诊断和治疗中的潜在应用是一个非常感兴趣的领域。目前的一个挑战是无法准确预测外源调节在潜在治疗性miRNAs水平上的功能后果。为了系统地解决这个问题，我们使用两个miRNAs(miR-7，miR-128)进行了miRNA转染实验。我们通过微阵列和定量(实时)聚合酶链式反应监测全球基因表达模式的变化。表达数据的网络分析被用来预测每一次转基因对细胞功能的影响，并对这些预测进行了实验验证。虽然数百到数千个基因表达模式的变化中约有20%可以归因于直接的miRNA-mRNA相互作用，但大多数变化是间接的，涉及miRNA介导的调控基因表达变化的下游后果。单个miRNAs诱导的基因表达变化在功能上是协调的，但在两个miRNAs之间是不同的。将MIR-7基因导入卵巢癌细胞后，细胞黏附和其他发育网络发生改变，这些改变以前与上皮-间充质转化(EMT)和其他与转移相关的过程有关。相反，miR-128的转染会导致细胞周期控制和其他通常与细胞复制相关的过程发生变化。不同的miRNAs家族所显示的基因表达的功能协调模式有可能为临床医生提供一种从系统而不是单基因的角度治疗癌症的策略。
MicroRNAs (miRNAs) are a class of small RNAs that have been linked to a number of diseases including cancer. The potential application of miRNAs in the diagnostics and therapeutics of ovarian and other cancers is an area of intense interest. A current challenge is the inability to accurately predict the functional consequences of exogenous modulations in the levels of potentially therapeutic miRNAs. In an initial effort to systematically address this issue, we conducted miRNA transfection experiments using two miRNAs (miR-7, miR-128). We monitored the consequent changes in global patterns of gene expression by microarray and quantitative (real-time) polymerase chain reaction. Network analysis of the expression data was used to predict the consequence of each transfection on cellular function and these predictions were experimentally tested. While ~20% of the changes in expression patterns of hundreds to thousands of genes could be attributed to direct miRNA-mRNA interactions, the majority of the changes are indirect, involving the downstream consequences of miRNA-mediated changes in regulatory gene expression. The changes in gene expression induced by individual miRNAs are functionally coordinated but distinct between the two miRNAs. MiR-7 transfection into ovarian cancer cells induces changes in cell adhesion and other developmental networks previously associated with epithelial-mesenchymal transitions (EMT) and other processes linked with metastasis. In contrast, miR-128 transfection induces changes in cell cycle control and other processes commonly linked with cellular replication. The functionally coordinated patterns of gene expression displayed by different families of miRNAs have the potential to provide clinicians with a strategy to treat cancers from a systems rather than a single gene perspective.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
3.8
作者：
Dickerson EB;Blackburn WH;Smith MH;Kapa LB;Lyon LA;McDonald JF
通讯作者：
McDonald JF
影响因子：
3
作者：
Mieczkowski J;Tyburczy ME;Dabrowski M;Pokarowski P
通讯作者：
Pokarowski P
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
13.6
作者：
Chan E;Prado DE;Weidhaas JB
通讯作者：
Weidhaas JB