miRNA-mRNA integrated analysis reveals roles for miRNAs in primary breast tumors.
miRNA-mRNA integrated analysis reveals roles for miRNAs in primary breast tumors.
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DOI：
10.1371/journal.pone.0016915
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发表时间：
2011-02-22
期刊：
影响因子：
3.7
通讯作者：
Børresen-Dale AL
中科院分区：
文献类型：
--
作者：
Enerly E;Steinfeld I;Kleivi K;Leivonen SK;Aure MR;Russnes HG;Rønneberg JA;Johnsen H;Navon R;Rødland E;Mäkelä R;Naume B;Perälä M;Kallioniemi O;Kristensen VN;Yakhini Z;Børresen-Dale AL
很少有研究同时对同一原发乳腺癌的miRNA和mRNA进行表达谱分析。在这项研究中，我们展示和分析了101个原发人类乳腺肿瘤中799个miRNAs的表达谱数据，以及全基因组mRNA谱和广泛的临床信息。我们研究了这些分子组成之间的关系，从它们之间的相互关系和临床特征。我们使用系统生物学的方法，通过统计浓缩的方法来检查miRNA和mRNAs之间的相关关系。我们发现miRNAs在分子固有亚型之间以及不同增殖水平的样本之间的表达存在统计学意义的差异。具体地说，我们指出miRNAs与TP53和ER状态显著相关。我们还发现，一些细胞过程，如增殖、细胞黏附和免疫反应，与某些miRNAs密切相关。我们使用细胞系上的高通量裂解微阵列验证了miRNAs在调控增殖中的作用，并指出了这一过程的潜在驱动因素。这项研究提供了一个全面的数据集以及方法和系统水平的结果，共同形成了进一步了解miRNA在原发性乳腺癌中的作用的工作的基础。
Few studies have performed expression profiling of both miRNA and mRNA from the same primary breast carcinomas. In this study we present and analyze data derived from expression profiling of 799 miRNAs in 101 primary human breast tumors, along with genome-wide mRNA profiles and extensive clinical information. We investigate the relationship between these molecular components, in terms of their correlation with each other and with clinical characteristics. We use a systems biology approach to examine the correlative relationship between miRNA and mRNAs using statistical enrichment methods. We identify statistical significant differential expression of miRNAs between molecular intrinsic subtypes, and between samples with different levels of proliferation. Specifically, we point to miRNAs significantly associated with TP53 and ER status. We also show that several cellular processes, such as proliferation, cell adhesion and immune response, are strongly associated with certain miRNAs. We validate the role of miRNAs in regulating proliferation using high-throughput lysate-microarrays on cell lines and point to potential drivers of this process. This study provides a comprehensive dataset as well as methods and system-level results that jointly form a basis for further work on understanding the role of miRNA in primary breast cancer.
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