College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.
Electrical and Computer Engineering, Seoul National University, Seoul 08826, Republic of Korea; Electrical Engineering, Korea University, Seoul 02841, Republic of Korea.
Methods. 2017 Oct 1;129:33-40. doi: 10.1016/j.ymeth.2017.03.017. Epub 2017 Mar 18.
A "miRNA sponge" is an artificial oligonucleotide-based miRNA inhibitor containing multiple binding sites for a specific miRNA. Each miRNA sponge can bind and sequester several miRNA copies, thereby decreasing the cellular levels of the target miRNA. In addition to developing artificial miRNA sponges, scientists have sought endogenous RNA transcripts and found that long non-coding RNAs, competing endogenous RNAs, pseudogenes, circular RNAs, and coding RNAs could act as miRNA sponges under precise conditions. Here we present a computational approach for the prediction of endogenous human miRNA sponge candidates targeting viral miRNAs derived from pathogenic human viruses. Viral miRNA binding sites were predicted using a newly-developed machine learning-based method, and candidate interactions between miRNAs and sponge RNAs were experimentally validated using luciferase reporter assay, western blot analysis, and flow cytometry. We found that BX649188.1 functions as a potential natural miRNA sponge against kshv-miR-K12-7-3p.
“miRNA 海绵”是一种基于人工寡核苷酸的 miRNA 抑制剂，包含多个与特定 miRNA 结合的位点。每个 miRNA 海绵可以结合并隔离几个 miRNA 拷贝，从而降低靶 miRNA 的细胞水平。除了开发人工 miRNA 海绵外，科学家们还寻找内源性 RNA 转录本，并发现长非编码 RNA、竞争内源性 RNA、假基因、环状 RNA 和编码 RNA 在特定条件下可以作为 miRNA 海绵。在这里，我们提出了一种计算方法，用于预测靶向来自致病性人类病毒的病毒 miRNA 的内源性人 miRNA 海绵候选物。使用新开发的基于机器学习的方法预测病毒 miRNA 结合位点，并使用荧光素酶报告基因分析、western blot 分析和流式细胞术实验验证 miRNA 和海绵 RNA 之间的候选相互作用。我们发现 BX649188.1 作为针对 kshv-miR-K12-7-3p 的潜在天然 miRNA 海绵起作用。
