Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China.
East Hospital, Dalian Medical University, 150 Jimo Road, Shanghai 200120, China.
Nat Commun. 2017 Jan 3;8:13964. doi: 10.1038/ncomms13964.
MicroRNAs (miRNAs) loss-of-function phenotypes are mainly induced by chemically modified antisense oligonucleotides. Here we develop an alternative inhibitor for miRNAs, termed 'small RNA zipper'. It is designed to connect miRNA molecules end to end, forming a DNA-RNA duplex through a complementary interaction with high affinity, high specificity and high stability. Two miRNAs, miR-221 and miR-17, are tested in human breast cancer cell lines, demonstrating the 70∼90% knockdown of miRNA levels by 30-50 nM small RNA zippers. The miR-221 zipper shows capability in rescuing the expression of target genes of miR-221 and reversing the oncogenic function of miR-221 in breast cancer cells. In addition, we demonstrate that the miR-221 zipper attenuates doxorubicin resistance with higher efficiency than anti-miR-221 in human breast cancer cells. Taken together, small RNA zippers are a miRNA inhibitor, which can be used to induce miRNA loss-of-function phenotypes and validate miRNA target genes.
微小 RNA（miRNA）功能丧失表型主要是由化学修饰的反义寡核苷酸诱导的。在这里，我们开发了一种 miRNA 的替代抑制剂，称为“小 RNA 拉链”。它被设计用来将 miRNA 分子连接起来，通过与高亲和力、高特异性和高稳定性的互补相互作用，形成 DNA-RNA 双链体。我们在人乳腺癌细胞系中测试了两种 miRNA，miR-221 和 miR-17，结果表明，30-50 nM 的小 RNA 拉链可以将 miRNA 水平降低 70∼90%。miR-221 拉链具有恢复 miR-221 靶基因表达并逆转 miR-221 在乳腺癌细胞中致癌功能的能力。此外，我们证明 miR-221 拉链在人乳腺癌细胞中比抗 miR-221 更有效地减弱阿霉素耐药性。总之，小 RNA 拉链是一种 miRNA 抑制剂，可用于诱导 miRNA 功能丧失表型和验证 miRNA 靶基因。
