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           Search results for: miRZip_885_5p anti_miR_885_5p microRNA construct   

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miR-19b enhances proliferation and apoptosis resistance via the EGFR signaling pathway by targeting PP2A and BIM in non-small cell lung cancer.

Epidermal growth factor receptor (EGFR) mutations enable constitutive active downstream signaling of PI3K/AKT, KRAS/ERK and JAK/STAT pathways, and promote tumor progression by inducing uncontrolled proliferation, evasion of apoptosis and migration of non-small cell lung cancer (NSCLC). In addition, such EGFR mutations increase the susceptibility of patients with NSCLC to tyrosine kinase inhibitor (TKI) therapy, but treated patients will invariably relapse with resistant disease. A global understanding of underlying molecular mechanisms of EGFR signaling may improve the management of NSCLC patients.

1038 related Products with: miR-19b enhances proliferation and apoptosis resistance via the EGFR signaling pathway by targeting PP2A and BIM in non-small cell lung cancer.

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Profiling of novel microRNAs elicited by EV71 and CA16 infection in human bronchial epithelial cells using high-throughput sequencing.

Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are two major etiologic agents associated with hand, foot, and mouth disease (HFMD) worldwide. Despite that they both belong to the Enterovirus genus of the Picornaviridae family, there are many differences in the infection process of these viruses. However, the underlying mechanisms have not been elucidated. Multiple studies indicated that microRNAs (miRNAs) can play critical roles in the host-pathogen interaction. Our previous study reported that EV71 and CA16 infection leads to differential expression of miRNAs in human bronchial epithelial (16HBE) cells. Herein, we aimed to further explore the expression profile and possible roles of other differentially expressed miRNAs in 16HBE cells following EV71 and CA16 infections using high-throughput sequencing. We describe 44 novel differentially expressed miRNAs in all samples. Among these miRNAs, 7 novel differentially expressed miRNAs show an opposite expression trend during the progression of EV71 and CA16 infections. Subsequently, bioinformatics analyses, including Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, were used to identify the biological processes, molecular functions, cellular components, and pathways involved. The top 10 significant GO and Pathway annotations indicated that 849 target genes are involved in cell development, such as nervous system development, multicellular organism development, and developmental biology. Finally, the genes identified in both the GO and Pathway analysis were used to construct a co-expression network to further identify the potential function of these co-expressed genes. Thus, our data may be beneficial in guiding further studies on the molecular mechanism of developmental regulation in HFMD pathogenesis caused by EV71 and CA16. In addition, it provided new candidate biomarkers or therapeutic targets for HFMD.

2044 related Products with: Profiling of novel microRNAs elicited by EV71 and CA16 infection in human bronchial epithelial cells using high-throughput sequencing.

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Transgene-Like Animal Models Using Intronic MicroRNAs.

Transgenic animal models are valuable tools for testing gene functions and drug mechanisms in vivo. They are also the best similitude for a human body for etiological and pathological research of diseases. All pharmaceutically developed medicines must be proven to be safe and effective in animals before approval by the Food and Drug Administration (FDA) to be used in clinical trials. To this end, the transgenic animal models of diseases serve as the front line of drug evaluation. However, there is currently no transgenic animal model for microRNA (miRNA)-related research. MiRNAs, small single-stranded regulatory RNAs capable of silencing intracellular gene transcripts (mRNAs) that contain either complete or partial complementarity to the miRNA, are useful for the design of new therapies against cancer polymorphism and viral mutation. Recently, varieties of natural miRNAs have been found to be derived from hairpin-like RNA precursors in almost all eukaryotes, including yeast (Schizosaccharomyces pombe), plant (Arabidopsis spp.), nematode (Caenorhabditis elegans), fly (Drosophila melanogaster), fish, mouse and human, involving intracellular defense against viral infections and regulation of certain gene expressions during development. To facilitate the miRNA research in vivo, we have developed a state-of-the-art transgenic strategy for silencing specific genes in zebrafish, chicken, and mouse, using intronic miRNAs. By the insertion of a hairpin-like pre-miRNA structure into the intron region of a gene, we have found that mature miRNAs were successfully transcribed by RNA polymerases type II (Pol-II), coexpressed with the encoding gene transcripts, and excised out of the encoding gene transcripts by intracellular RNA splicing and processing mechanisms. In conjunction with retroviral transfection, the designed hairpin-like pre-miRNA construct has also been placed in the intron regions of a cellular gene for tissue-specific expression, specifically regulated by the gene promoter of interest. Because the retroviral vectors are integrated into the genome of its host cells, we can select and propagate the most effective transgenic animals to form a stable model line for further research. Here, we have shown for the first time that transgene-like animal models were generated using the intronic miRNA expression system reported previously, which has been proven to be useful for studying miRNA function as well as the related gene regulation in vivo.

2707 related Products with: Transgene-Like Animal Models Using Intronic MicroRNAs.

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Unraveling the determinants of microRNA mediated regulation using a massively parallel reporter assay.

Despite extensive research, the sequence features affecting microRNA-mediated regulation are not well understood, limiting our ability to predict gene expression levels in both native and synthetic sequences. Here we employed a massively parallel reporter assay to investigate the effect of over 14,000 rationally designed 3' UTR sequences on reporter construct repression. We found that multiple factors, including microRNA identity, hybridization energy, target accessibility, and target multiplicity, can be manipulated to achieve a predictable, up to 57-fold, change in protein repression. Moreover, we predict protein repression and RNA levels with high accuracy (R = 0.84 and R = 0.80, respectively) using only 3' UTR sequence, as well as the effect of mutation in native 3' UTRs on protein repression (R = 0.63). Taken together, our results elucidate the effect of different sequence features on miRNA-mediated regulation and demonstrate the predictability of their effect on gene expression with applications in regulatory genomics and synthetic biology.

1383 related Products with: Unraveling the determinants of microRNA mediated regulation using a massively parallel reporter assay.

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Exploring the Potential Application of Short Non-Coding RNA-Based Genetic Circuits in Chinese Hamster Ovary Cells.

The majority of cell engineering for recombinant protein production to date has relied on traditional genetic engineering strategies, such as gene overexpression and gene knock-outs, to substantially improve the production capabilities of Chinese Hamster Ovary (CHO) cells. However, further improvements in cellular productivity or control over product quality is likely to require more sophisticated rational approaches to coordinate and balance cellular pathways. For these strategies to be implemented, novel molecular tools need to be developed to facilitate more refined control of gene expression. Multiple gene control strategies are developed over the last decades in the field of synthetic biology, including DNA and RNA-based systems, which allows tight and timely control over gene expression. microRNAs has received a lot of attention over the last decade in the CHO field and are used to engineer and improve CHO cells. In this review we focus on microRNA-based gene control systems and discuss their potential use as tools rather than targets in order to gain better control over gene expression.

2061 related Products with: Exploring the Potential Application of Short Non-Coding RNA-Based Genetic Circuits in Chinese Hamster Ovary Cells.

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The regulatory network analysis of long noncoding RNAs in human colorectal cancer.

Colorectal cancer (CRC) is among one of the most prevalent and lethiferous diseases worldwide. Long noncoding RNAs (lncRNAs) are commonly accepted to function as a key regulatory factor in human cancer, but the potential regulatory mechanisms of CRC-associated lncRNA are largely obscure. Here, we integrated several expression profiles to obtain 55 differentially expressed (DE) lncRNAs. We first detected lncRNA interactions with transcription factors, microRNAs, mRNAs, and RNA-binding proteins to construct a regulatory network and then create functional enrichment analyses for them using bioinformatics approaches. We found the upregulated genes in the regulatory network are enriched in cell cycle and DNA damage response, while the downregulated genes are enriched in cell differentiation, cellular response, and cell signaling. We then employed module-based methods to mine several intriguing modules from the overall network, which helps to classify the functions of genes more specifically. Next, we confirmed the validity of our network by comparisons with a randomized network using computational method. Finally, we attempted to annotate lncRNA functions based on the regulatory network, which indicated its potential application. Our study of the lncRNA regulatory network provided significant clues to unveil lncRNAs potential regulatory mechanisms in CRC and laid a foundation for further experimental investigation.

1214 related Products with: The regulatory network analysis of long noncoding RNAs in human colorectal cancer.

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The Bioinformatic Analysis of the Dysregulated Genes and MicroRNAs in Entorhinal Cortex, Hippocampus, and Blood for Alzheimer's Disease.

The incidence of Alzheimer's disease (AD) has been increasing in recent years, but there exists no cure and the pathological mechanisms are not fully understood. This study aimed to find out the pathogenesis of learning and memory impairment, new biomarkers, potential therapeutic targets, and drugs for AD.

2645 related Products with: The Bioinformatic Analysis of the Dysregulated Genes and MicroRNAs in Entorhinal Cortex, Hippocampus, and Blood for Alzheimer's Disease.

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Construction of an oesophageal cancer-specific ceRNA network based on miRNA, lncRNA, and mRNA expression data.

To explore the expression profiles of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and mRNAs in oesophageal squamous cell carcinoma (ESCC) in order to construct an oesophageal cancer-specific competing endogenous RNA (ceRNA) network.

1209 related Products with: Construction of an oesophageal cancer-specific ceRNA network based on miRNA, lncRNA, and mRNA expression data.

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miR-200a-3p promotes b-Amyloid-induced neuronal apoptosis through down-regulation of SIRT1 in Alzheimer's disease.

The aberrantly expressed microRNAs (miRNAs) including miR-200a-3p have been reported in the brains of Alzheimer's disease (AD) patients in recent researches. Nevertheless, the role of miR-200a-3p in AD has not been characterized. The purpose of this study was to examine whether miR-200a-3p regulated β-Ameyloid (A β)-induced neuronal apoptosis by targeting SIRT1, a known anti-apoptotic protein. An increased level of miR-200a-3p and a decreased level of SIRT1 in the hippocampus of APPswe/PS delta E9 mice (a model for AD) were observed. To construct an in vitro cell model of AD, PC12 cells were cultured in presence of A β. The results of flow cytometry analysis showed that the apoptosis rate and cleaved-caspase-3 expression in PC12 cells exposed to A βwere remarkably increased, but the apoptosis rate and cleaved-caspase-3 activity were decreased when cells were transfected with anti-miR-200a-3p. On the other hand, MTT assay showed that the cell survival rate was increased in the A β+ anti-miR-200a-3p group compared with the A β+ anti-miR-NC group. Dual-luciferase reporter gene assay validated the predicted miR-200a-3p binding sites in the 3'- UTR of SIRT1 mRNA. In addition, downregulation of SIRT1 promoted A β-induced neuronal apoptosis and cleavedcaspase- 3 level in PC12 cells, whereas anti-miR-200a-3p reversed these effects. Knockdown of SIRT1 decreased the inhibitory effect of A βon cell viability, while anti-miR-200a-3p attenuated this effect. Overall, the results suggest that suppression of miR-200a-3p attenuates A β-induced apoptosis in PC12 cells by targeting SIRT1. Thus, miR-200a-3p may be a potential therapeutic target for treatment of AD.

1318 related Products with: miR-200a-3p promotes b-Amyloid-induced neuronal apoptosis through down-regulation of SIRT1 in Alzheimer's disease.

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Translational systems pharmacology-based predictive assessment of drug-induced cardiomyopathy.

Drug-induced cardiomyopathy contributes to drug attrition. We compared two pipelines of predictive modeling: (1) applying elastic net (EN) to differentially expressed genes (DEGs) of drugs; (2) applying integer linear programming (ILP) to construct each drug's signaling pathway starting from its targets to downstream proteins, to transcription factors, and to its DEGs in human cardiomyocytes, and then subjecting the genes/proteins in the drugs' signaling networks to EN regression. We classified 31 drugs with availability of DEGs into 13 toxic and 18 nontoxic drugs based on a clinical cardiomyopathy incidence cutoff of 0.1%. The ILP-augmented modeling increased prediction accuracy from 79% to 88% (sensitivity: 88%; specificity: 89%) under leave-one-out cross validation. The ILP-constructed signaling networks of drugs were better predictors than DEGs. Per literature, the microRNAs that reportedly regulate expression of our six top predictors are of diagnostic value for natural heart failure or doxorubicin-induced cardiomyopathy. This translational predictive modeling might uncover potential biomarkers.

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