Validated MicroRNA Target Databases: An Evaluation.
Validated MicroRNA Target Databases: An Evaluation.
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DOI：
10.1002/ddr.21278
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发表时间：
2015-11
影响因子：
3.8
通讯作者：
Witwer KW
中科院分区：
文献类型：
--
作者：
Lee YJ;Kim V;Muth DC;Witwer KW
来自临床前和临床研究的积极发现，包括消耗或补充microRNA (miRNA)，使人们对基于miRNA的治疗方法持乐观态度。然而，必须考虑脱靶效应。预测这些影响是复杂的。每个miRNA可能靶向许多基因转录物，并且控制不完全互补的miRNA与靶标相互作用的规则尚未完全了解。几个数据库提供了相对少量实验证实的miRNA靶对的列表。虽然不完整，但这一信息至少可以评估一些脱靶效应。我们使用50个按字母顺序连续的基因列表评估了四个实验验证的miRNA数据库的性能：目标相互作用（miRWalk 2.0, miRTarBase， miRecords和TarBase 7.0）。我们检查了所提供的引文，以确定每种相互作用在实验上得到支持的程度。为了评估稳定性，我们在五个月的开始和结束时进行了测试。不同数据库的结果差异很大。其中两个数据库在五个月的时间里发生了显著变化。大多数报道的miRNA与靶标相互作用的证据是间接的或其他微弱的，相对较少的相互作用被多个出版物支持。一些返回的结果似乎是由简单的文本搜索产生的，这些搜索没有提供对搜索词之间关系的深入了解，甚至可能不包括所报告的基因或miRNA，因此可能是无效的。我们得出结论，验证数据库提供了重要的信息，但并非所有现有数据库中的所有信息都是最新的或准确的。然而，更全面的验证数据库可能为研究小RNA疗法的脱靶效应提供有用的起点。
Positive findings from pre-clinical and clinical studies involving depletion or supplementation of microRNA (miRNA) engender optimism about miRNA–based therapeutics. However, off-target effects must be considered. Predicting these effects is complicated. Each miRNA may target many gene transcripts, and the rules governing imperfectly complementary miRNA:target interaction are incompletely understood. Several databases provide lists of the relatively small number of experimentally confirmed miRNA:target pairs. Although incomplete, this information might allow assessment of at least some of the off-target effects. We evaluated the performance of four databases of experimentally validated miRNA:target interactions (miRWalk 2.0, miRTarBase, miRecords, and TarBase 7.0) using a list of 50 alphabetically consecutive genes. We examined the provided citations to determine the degree to which each interaction was experimentally supported. To assess stability, we tested at the beginning and end of a five month period. Results varied widely by database. Two of the databases changed significantly over the course of five months. Most reported evidence for miRNA:target interactions was indirect or otherwise weak, and relatively few interactions were supported by more than one publication. Some returned results appear to arise from simplistic text searches that offer no insight into the relationship of the search terms, may not even include the reported gene or miRNA, and may thus be invalid. We conclude that validation databases provide important information, but not all information in all extant databases is up-to-date or accurate. Nevertheless, the more comprehensive validation databases may provide useful starting points for investigation of off-target effects of proposed small RNA therapies.