title: Small RNA zippers lock miRNA molecules and block miRNA function in mammalian cells.
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.
authors.affiliation: 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.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Meng
authors.affiliation: 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.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Liu
authors.affiliation: 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.|School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Lü
authors.affiliation: 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.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Shengqiong
authors.initials: S
authors.lastname: Deng
authors.affiliation: 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.
authors.forename: Guangxue
authors.initials: G
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Qiao
authors.affiliation: 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.
authors.forename: Chuyi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Lixiao
authors.initials: L
authors.lastname: Zhen
authors.affiliation: 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Wenshu
authors.initials: W
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Pestell
authors.affiliation: 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.
authors.forename: Huiming
authors.initials: H
authors.lastname: Fan
authors.affiliation: 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.
authors.forename: Yi-Han
authors.initials: YH
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Zuoren
authors.identifier: 0000-0003-4196-9662
authors.initials: Z
authors.lastname: Yu
mesh_terms: D000070416:Antagomirs / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism*; D052157:Aptamers, Nucleotide / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014741:Video Recording
chemical_list: D000070416:Antagomirs; D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D050760:Cyclin-Dependent Kinase Inhibitor p27; D035683:MicroRNAs; C524941:MIRN17 microRNA, human; C525709:MIR221, human