Screening and validation of lncRNAs and circRNAs as miRNA sponges
Screening and validation of lncRNAs and circRNAs as miRNA sponges
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DOI：
10.1093/bib/bbw053
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发表时间：
2017-09-01
影响因子：
9.5
通讯作者：
Uchida, Shizuka
中科院分区：
文献类型：
--
作者：
Militello, Giuseppe;Weirick, Tyler;Uchida, Shizuka
过去二十年的深入研究揭示了非编码 RNA (ncRNA) 的存在和重要性，其中包括 microRNA (miR) 和长 ncRNA (lncRNA)。这两类 ncRNA 在一定程度上相互作用，因为一些 lncRNA 与 miR 结合以隔离它们。此类 lncRNA 统称为“竞争性内源 RNA”或“miRNA 海绵”。在这项研究中，我们利用公开的数据集和数据库筛选了可以充当 miRNA 海绵的 lncRNA。为了揭示 miRNA 海绵的作用，进行了功能丧失实验，揭示了 miRNA 海绵的生物学作用。 LINC00324 通过与 miR-615-5p 结合，导致其靶标 BTG2 去抑制，对细胞存活非常重要。 LOC400043 通过隔离 miR-28-3p 和 miR-96-5p 来控制多种生物学功能，从而改变转录调节因子的表达。最后，我们还筛选了可能充当 miRNA 海绵的环状 RNA (circRNA)。至少本研究中选定的 circRNA 的结果是阴性的。总之，miRNA海绵可以通过应用一系列生物信息学技术来识别，并通过生物学实验进行验证。
Intensive research in past two decades has uncovered the presence and importance of noncoding RNAs (ncRNAs), which includes microRNAs (miRs) and long ncRNAs (lncRNAs). These two classes of ncRNAs interact to a certain extent, as some lncRNAs bind to miRs to sequester them. Such lncRNAs are collectively called 'competing endogenous RNAs' or 'miRNA sponges'. In this study, we screened for lncRNAs that may act as miRNA sponges using the publicly available data sets and databases. To uncover the roles of miRNA sponges, loss-of-function experiments were conducted, which revealed the biological roles as miRNA sponges. LINC00324 is important for the cell survival by binding to miR-615-5p leading to the derepression of its target BTG2. LOC400043 controls several biological functions via sequestering miR-28-3p and miR-96-5p, thereby changing the expressions of transcriptional regulators. Finally, we also screened for circular RNAs (circRNAs) that may function as miRNA sponges. The results were negative at least for the selected circRNAs in this study. In conclusion, miRNA sponges can be identified by applying a series of bioinformatics techniques and validated with biological experiments.