Integrative genomic analyses reveal clinically relevant long noncoding RNAs in human cancer.

Integrative genomic analyses reveal clinically relevant long noncoding RNAs in human cancer.
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DOI:
10.1038/nsmb.2591
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发表时间:
2013-07
影响因子:
16.8
通讯作者:
Liu, X. Shirley
Liu, X. Shirley
中科院分区:
生物学1区
文献类型:
--
作者:
Du, Zhou;Fei, Teng;Verhaak, Roel G. W.;Su, Zhen;Zhang, Yong;Brown, Myles;Chen, Yiwen;Liu, X. Shirley

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尽管人们越来越认识到长链非编码RNA(lncRNA)在正常生理和疾病中的重要性,但我们对癌症相关lncRNA的认识仍然有限。通过重新利用微阵列探针,我们构建了四种不同癌症类型的约1,300个肿瘤中10,207个lncRNA基因的表达谱。通过对lncRNA表达谱与临床结果和体细胞拷贝数改变(SCNA)的综合分析,我们鉴定了与癌症亚型和临床预后相关的lncRNA,并预测了那些是癌症进展的潜在驱动因素。我们通过实验证实前列腺癌细胞生长依赖于两种新的lncRNA来验证我们的预测。我们的分析为lncRNA生物标志物的开发和lncRNA治疗靶点的鉴定提供了临床相关的lncRNA资源。它还展示了整合医学上可用的基因组数据集和临床信息以发现疾病相关lncRNA的能力。
Despite growing appreciations of the importance of long non-coding RNA (lncRNA) in normal physiology and disease, our knowledge of cancer-related lncRNA remains limited. By repurposing microarray probes, we constructed the expression profile of 10,207 lncRNA genes in approximately 1,300 tumors over four different cancer types. Through integrative analysis of the lncRNA expression profiles with clinical outcome and somatic copy number alteration (SCNA), we identified lncRNA that are associated with cancer subtypes and clinical prognosis, and predicted those that are potential drivers of cancer progression. We validated our predictions by experimentally confirming prostate cancer cell growth dependence on two novel lncRNA. Our analysis provided a resource of clinically relevant lncRNA for development of lncRNA biomarkers and identification of lncRNA therapeutic targets. It also demonstrated the power of integrating publically available genomic datasets and clinical information for discovering disease associated lncRNA.
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