Small RNA zippers lock miRNA molecules and block miRNA function in mammalian cells

Lingyu Meng, Cuicui Liu, Jinhui Lü, Qian Zhao, Shengqiong Deng, Guangxue Wang, Jing Qiao, Chuyi Zhang, Lixiao Zhen, Ying Lu, Wenshu Li, Yuzhen Zhang, Richard G. Pestell, Huiming Fan, Yi-Han Chen, Zhongmin Liu and Zuoren Yu ()
Additional contact information
Lingyu Meng: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine
Cuicui Liu: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine
Jinhui Lü: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine
Qian Zhao: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine
Shengqiong Deng: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine
Guangxue Wang: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine
Jing Qiao: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine
Chuyi Zhang: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine
Lixiao Zhen: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine
Ying Lu: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine
Wenshu Li: School of Basic Medical Sciences, Wenzhou Medical University
Yuzhen Zhang: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine
Richard G. Pestell: Sidney Kimmel Cancer Center, Thomas Jefferson University
Huiming Fan: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine
Yi-Han Chen: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine
Zhongmin Liu: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine
Zuoren Yu: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms13964

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