Comprehensive analysis of long non-coding RNAs in human breast cancer clinical subtypes.
Comprehensive analysis of long non-coding RNAs in human breast cancer clinical subtypes.
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DOI：
10.18632/oncotarget.2454
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发表时间：
2014-10-30
期刊：
影响因子：
--
通讯作者：
Esteva FJ
中科院分区：
文献类型：
--
作者：
Su X;Malouf GG;Chen Y;Zhang J;Yao H;Valero V;Weinstein JN;Spano JP;Meric-Bernstam F;Khayat D;Esteva FJ
越来越多的证据表明长链非编码RNA（lncRNA）作为生物标志物和治疗靶点在实体瘤中的潜在作用。然而，lncRNA表达在人类乳腺癌生物学、预后和分子分类中的作用仍然未知。在此，我们从癌症基因组图谱项目中建立了658例乳腺浸润性导管癌的lncRNA谱。我们发现lncRNA表达与人乳腺上皮细胞（未转化）和乳腺癌细胞系MCF-7的基因表达和染色质景观相关。lncRNA的无监督共识聚类显示了四个亚组，显示出不同的差异。顺式和反式作用lncRNA的基因集富集分析显示，乳腺癌发生的主调节因子驱动的乳腺癌特征富集。有趣的是，lncRNA HOTAIR在HER 2富集亚组中显著过表达，而lncRNA HOTAIRM 1在基底样亚组中显著过表达。雌激素受体（ESR 1）表达与lncRNA簇III和IV中不同的lncRNA网络相关。重要的是，几乎三分之二的lncRNA被增强子染色质修饰标记（即，H3 K27 ac），这表明乳腺癌中表达的lncRNA通过邻近基因的活性增加来驱动致癌作用。总之，我们的研究描述了乳腺癌中的第一个lncRNA亚型分类，并为未来的研究提供了框架，以评估lncRNA和乳腺癌表观基因组之间的相互作用。
Accumulating evidence highlights the potential role of long non-coding RNAs (lncRNAs) as biomarkers and therapeutic targets in solid tumors. However, the role of lncRNA expression in human breast cancer biology, prognosis and molecular classification remains unknown. Herein, we established the lncRNA profile of 658 infiltrating ductal carcinomas of the breast from The Cancer Genome Atlas project. We found lncRNA expression to correlate with the gene expression and chromatin landscape of human mammary epithelial cells (non-transformed) and the breast cancer cell line MCF-7. Unsupervised consensus clustering of lncRNA revealed four subgroups that displayed different prognoses. Gene set enrichment analysis for cis- and trans-acting lncRNAs showed enrichment for breast cancer signatures driven by master regulators of breast carcinogenesis. Interestingly, the lncRNA HOTAIR was significantly overexpressed in the HER2-enriched subgroup, while the lncRNA HOTAIRM1 was significantly overexpressed in the basal-like subgroup. Estrogen receptor (ESR1) expression was associated with distinct lncRNA networks in lncRNA clusters III and IV. Importantly, almost two thirds of the lncRNAs were marked by enhancer chromatin modifications (i.e., H3K27ac), suggesting that expressed lncRNA in breast cancer drives carcinogenesis through increased activity of neighboring genes. In summary, our study depicts the first lncRNA subtype classification in breast cancer and provides the framework for future studies to assess the interplay between lncRNAs and the breast cancer epigenome.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
4.3
作者：
Dinger ME;Pang KC;Mercer TR;Mattick JS
通讯作者：
Mattick JS
影响因子：
11.1
作者：
Holland, Daniel G.;Burleigh, Angela;Git, Anna;Goldgraben, Mae A.;Perez-Mancera, Pedro A.;Chin, Suet-Feung;Hurtado, Antonio;Bruna, Alejandro;Ali, H. Raza;Greenwood, Wendy;Dunning, Mark J.;Samarajiwa, Shamith;Menon, Suraj;Rueda, Oscar M.;Lynch, Andy G.;McKinney, Steven;Ellis, Ian O.;Eaves, Connie J.;Carroll, Jason S.;Curtis, Christina;Aparicio, Samuel;Caldas, Carlos
通讯作者：
Caldas, Carlos
影响因子：
--
作者：
Crea F;Watahiki A;Quagliata L;Xue H;Pikor L;Parolia A;Wang Y;Lin D;Lam WL;Farrar WL;Isogai T;Morant R;Castori-Eppenberger S;Chi KN;Wang Y;Helgason CD
通讯作者：
Helgason CD
影响因子：
3.8
作者：
Lu, Lingeng;Zhu, Gongjian;Yu, Herbert
通讯作者：
Yu, Herbert