Wang Junyi, Ma Ruixia, Ma Wei, Chen Ji, Yang Jichun, Xi Yaguang, Cui Qinghua
Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University, 38 Xueyuan Rd, Beijing 100191, China MOE Key Lab of Cardiovascular Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Mitchell Cancer Institute, University of South Alabama, 1160 Springhill Ave, Mobile, AL 36604, USA.
Nucleic Acids Res. 2016 May 19;44(9):e90. doi: 10.1093/nar/gkw093. Epub 2016 Feb 16.
LncRNAs represent a large class of noncoding RNA molecules that have important functions and play key roles in a variety of human diseases. There is an urgent need to develop bioinformatics tools as to gain insight into lncRNAs. This study developed a sequence-based bioinformatics method, LncDisease, to predict the lncRNA-disease associations based on the crosstalk between lncRNAs and miRNAs. Using LncDisease, we predicted the lncRNAs associated with breast cancer and hypertension. The breast-cancer-associated lncRNAs were studied in two breast tumor cell lines, MCF-7 and MDA-MB-231. The qRT-PCR results showed that 11 (91.7%) of the 12 predicted lncRNAs could be validated in both breast cancer cell lines. The hypertension-associated lncRNAs were further evaluated in human vascular smooth muscle cells (VSMCs) stimulated with angiotensin II (Ang II). The qRT-PCR results showed that 3 (75.0%) of the 4 predicted lncRNAs could be validated in Ang II-treated human VSMCs. In addition, we predicted 6 diseases associated with the lncRNA GAS5 and validated 4 (66.7%) of them by literature mining. These results greatly support the specificity and efficacy of LncDisease in the study of lncRNAs in human diseases. The LncDisease software is freely available on the Software Page: http://www.cuilab.cn/.
长链非编码RNA（lncRNAs）是一大类非编码RNA分子，它们具有重要功能，在多种人类疾病中发挥关键作用。迫切需要开发生物信息学工具来深入了解lncRNAs。本研究开发了一种基于序列的生物信息学方法LncDisease，用于基于lncRNAs与微小RNA（miRNAs）之间的相互作用来预测lncRNA-疾病关联。使用LncDisease，我们预测了与乳腺癌和高血压相关的lncRNAs。在两种乳腺肿瘤细胞系MCF-7和MDA-MB-231中研究了与乳腺癌相关的lncRNAs。定量逆转录聚合酶链反应（qRT-PCR）结果表明，12个预测的lncRNAs中有11个（91.7%）在两种乳腺癌细胞系中均可得到验证。在血管紧张素II（Ang II）刺激的人血管平滑肌细胞（VSMCs）中进一步评估了与高血压相关的lncRNAs。qRT-PCR结果表明，4个预测的lncRNAs中有3个（75.0%）在Ang II处理的人VSMCs中可得到验证。此外，我们预测了与lncRNA GAS5相关的6种疾病，并通过文献挖掘验证了其中4种（66.7%）。这些结果极大地支持了LncDisease在人类疾病lncRNAs研究中的特异性和有效性。LncDisease软件可在软件页面免费获取：http://www.cuilab.cn/ 。
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