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Small RNA zippers lock miRNA molecules and block miRNA function i | 10241
Transcriptomics: Open Access

Transcriptomics: Open Access
Open Access

ISSN: 2329-8936

+44 1223 790975

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


2nd International Conference on Molecular Biology, Nucleic Acids & Molecular Medicine

August 31-September 01, 2017 Philadelphia, USA

Zuoren Yu, Lingyu Meng and Qian Zhao

Tongji University School of Medicine, China

Posters & Accepted Abstracts: Transcriptomics

Abstract :

Small non-coding RNA-based diagnostic and therapeutic applications for human cancer are expected soon. Knocking down the expression level or blocking the function of oncogenic miRNAs is believed to be a promising strategy for cancer treatment. miRNAs loss-of-function phenotypes are mainly induced by chemically modified antisense oligonucleotides. Here, we develop an alternative inhibitor for miRNAs, termed as small RNA zipper. It is designed to bind to the 5��?-half sequences of one molecule and the 3��?-half sequences of another molecule of the target miRNA through a complementary interaction. The small RNA zipper can connect the target miRNA molecules end to end forming a DNA��?RNA duplex with high affinity, high specificity and high stability. To avoid self-complementarity and to enhance binding specificity, LNA nucleosides were applied to synthesize the small RNA zipper. Two miRNAs, miR-221 and miR-17, were tested in human breast cancer cell lines, demonstrating the 70%-90% knockdown of miRNA levels by 30��?50 nM small RNA zippers at 24-48 h after transfection. The effect of the miRNA zipper was not limited to the target miRNA, but also to the expression of iso-miRNAs. Let-7 family members and point mutated sequence were applied to further validate the specificity of the miRNA 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 novel type of miRNA inhibitors, which can be used to induce miRNA loss-of-function phenotypes and validate miRNA target genes.

Biography :

Zuoren Yu is currently a Professor at Tongji University School of Medicine, Research Center for Translational, Shanghai East Hospital. After obtaining PhD degree in 2003 from Chinese Academy of Medical Sciences, he started Post-doctoral training at University of Pennsylvania School of Medicine and Thomas Jefferson University Kimmel Cancer Center. In 2009, he was assigned for a Faculty position in the track of Research Assistant Professor at Thomas Jefferson University. After joining Tongji University in Shanghai in 2012, he has been focusing on non-coding RNA regulation of breast cancer stem cells related with drug sensitivity, tumour regeneration and cancer metastasis. His main research work includes: Finding cell cycle regulator CCND1 is involved in the regulation of miRNA biogenesis and histone H3K9 tri-methylation, finding a regulatory loop between CCND1 and miR-17/20 in breast cancer, and demonstrating a microenvironment-mediated heterotypic signalling through which miR-17/20 regulate cross talking between cancer cells and inhibit breast cancer cell migration and metastasis.

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