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

Meng, Lingyu; Liu, Cuicui; Lu, Jianrong; Zhao, Qian; Deng, Shengqiong; Wang, Guangxue; Qiao, Jing; Zhang, Chuyi; Zhen, Lixiao; Lü, Ying; Li, Wenshu; Zhang, Yuzhen; Pestell, Richard G.; Fan, Huishou; Chen, Yi Han; Liu, Zhongmin; Yu, Zuoren

doi:10.1038/ncomms13964

Cited by 52 publications

(44 citation statements)

References 29 publications

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“…Therefore, the decrease of miRNA-122 levels in the experiments where molecular sponges were transfected demonstrates functional sequestration. Similar effects on miRNA levels detected by RT-qPCR were recently reported for sequestration of miRNA-17 and -221 by small RNA zippers [ 26 ].…”

supporting

confidence: 84%

Functional sequestration of microRNA-122 from Hepatitis C Virus by circular RNA sponges

et al. 2018

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Circular RNAs (circRNAs) were recently described as a novel class of cellular RNAs. Two circRNAs were reported to function as molecular sponges, sequestering specific microRNAs, thereby de-repressing target mRNAs. Due to their elevated stability in comparison to linear RNA, circRNAs may be an interesting tool in molecular medicine and biology. In this study, we provide a proof-of-principle that circRNAs can be engineered as microRNA sponges. As a model system, we used the Hepatitis C Virus (HCV), which requires cellular microRNA-122 for its life cycle. We produced artificial circRNA sponges in vitro that efficiently sequester microRNA-122, thereby inhibiting viral protein production in an HCV cell culture system. These circRNAs are more stable than their linear counterparts, and localize both to the cytoplasm and to the nucleus, opening up a wide range of potential applications.

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supporting

confidence: 84%

Functional sequestration of microRNA-122 from Hepatitis C Virus by circular RNA sponges

et al. 2018

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“…There are two types of miRNA targets: mRNAs with near perfect complementarity to the miRNA and mRNAs with limited complementarity to the miRNA [6,7]. miRNAs function in diverse physiological processes and an increasing number of studies have proven that miRNAs play vital roles in carcinogenesis by regulating gene expression through mechanisms including deletion, amplification, mutation of miRNA locus, and epigenetic silencing of miR-RNA target genes [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

miR-1204 targets VDR to promotes epithelial-mesenchymal transition and metastasis in breast cancer

Liu

Wang

et al. 2018

Oncogene

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Plasmacytoma variant translocation 1 (PVT1) is an lncRNA that plays vital roles in breast cancer (BC) pathogenesis. Increasing evidence suggests that miRNAs that reside in the PVT1 locus are the main driver of the oncogenic roles of PVT1 in cancer. However, the oncogenic role and underlying mechanism of miR-1204, located in the PVT1 locus, in human cancer is still unclear. In this study, we discovered that increased expression of miR-1204 is associated with poor prognosis in BC. Moreover, miR-1204 promotes proliferation, epithelial-mesenchymal transition and invasion of BC cells both in vitro and in vivo. Mechanistic investigations demonstrated that VDR is a novel target gene of miR-1204. Interference of VDR restored miR-1204-mediated BC cell proliferation, tumorigenesis, and metastasis. Collectively, our results demonstrated that the miR-1204-VDR pathway exerts oncogenic effects in BC with potential therapeutic applications in blocking BC development and progression.

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“…They found that B-cell chronic lymphocytic leukemia (B-CLL) cell viability is gradually decreased over time after the inhibition of miR-222; they showed that the viability of LNA-anti-miR222–transfected cells was <47% of untreated cells at 72 h post-transfection. A small LNA, termed small RNA zipper, has been developed to inhibit miRNA by generating a DNA–RNA duplex through a complementary interaction with high affinity, specificity, and stability [ 69 ]. The small RNA zipper is a small LNA in which half of its sequence is complementary to the 5′-end of the target miRNA, and the other half is complementary to the 3′-end.…”

Section: Oncomir-targeting Strategiesmentioning

confidence: 99%

“…The small RNA zipper is a small LNA in which half of its sequence is complementary to the 5′-end of the target miRNA, and the other half is complementary to the 3′-end. All individual mature miRNAs can be connected end to end via the small RNA zipper following the zipper strategy ( Figure 3 ) [ 69 ]. For targeting miR-221 and miR-17, a concentration of 30–50 nM of small RNA zippers achieves a 70–90% knockdown of miRNA in human breast cancer cell lines [ 69 ].…”

Section: Oncomir-targeting Strategiesmentioning

confidence: 99%

Development of Novel Therapeutic Agents by Inhibition of Oncogenic MicroRNAs

Nguyen

Chang

2017

IJMS

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MicroRNAs (miRs, miRNAs) are regulatory small noncoding RNAs, with their roles already confirmed to be important for post-transcriptional regulation of gene expression affecting cell physiology and disease development. Upregulation of a cancer-causing miRNA, known as oncogenic miRNA, has been found in many types of cancers and, therefore, represents a potential new class of targets for therapeutic inhibition. Several strategies have been developed in recent years to inhibit oncogenic miRNAs. Among them is a direct approach that targets mature oncogenic miRNA with an antisense sequence known as antimiR, which could be an oligonucleotide or miRNA sponge. In contrast, an indirect approach is to block the biogenesis of miRNA by genome editing using the CRISPR/Cas9 system or a small molecule inhibitor. The development of these inhibitors is straightforward but involves significant scientific and therapeutic challenges that need to be resolved. In this review, we summarize recent relevant studies on the development of miRNA inhibitors against cancer.

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

Cited by 52 publications

References 29 publications

Functional sequestration of microRNA-122 from Hepatitis C Virus by circular RNA sponges

Functional sequestration of microRNA-122 from Hepatitis C Virus by circular RNA sponges

miR-1204 targets VDR to promotes epithelial-mesenchymal transition and metastasis in breast cancer

Development of Novel Therapeutic Agents by Inhibition of Oncogenic MicroRNAs

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