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https://www.readbyqxmd.com/read/27927008/microrna-296-5p-promotes-invasiveness-through-downregulation-of-nerve-growth-factor-receptor-and-caspase-8
#1
Hong Lee, Chang Hoon Shin, Hye Ree Kim, Kyung Hee Choi, Hyeon Ho Kim
Glioblastomas (GBM) are very difficult to treat and their aggressiveness is one of the main reasons for this as well as for the frequent recurrences. MicroRNAs posttranscriptionally regulate their target genes through interaction between their seed sequence and 3'UTR of the target mRNAs. We previously reported that miR-296-3p is regulated by neurofibromatosis 2 (NF2) and enhances the invasiveness of GBM cells via SOCS2/STAT3. In this study, we investigated whether miR-296-5p, which originates from the same precursor miRNA as miR-296-3p, can increase the invasiveness of GBM cells...
December 8, 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27925331/the-mirna-landscape-of-colorectal-polyps
#2
Martha L Slattery, Jennifer S Herrick, Roger K Wolff, Lila E Mullany, John R Stevens, Wade Samowitz
The genomic landscape of adenomas and polyps may help define disease pathways. Expression of miRNAs in adenomas and polyps may importantly contribute to these pathways. We evaluated miRNA expression in 293 polyp-normal colorectal mucosa pairs. Polyps were classified as either adenomatous polyp (AD), hyperplastic polyp (HP), or sessile serrated polyp (SSP). We compared these miRNA expression profiles in polyps to miRNA expression in microsatellite unstable (MSI) and stable (MSS) tumors. A False Discovery Rate (FDR) of 0...
December 7, 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27925170/associations-of-microrna-single-nucleotide-polymorphisms-and-disease-risk-and-pathophysiology
#3
REVIEW
Xiaoxiao Liu, Zhijun Han, Chengjian Yang
Single nucleotide polymorphisms (SNPs) are genetic variations that contribute to human phenotypes associated with various diseases. SNPs are involved in the regulation of a broad range of physiological and pathological processes, such as cellular senescence, apoptosis, inflammation, and immune response, by up-regulating the expression of classical inflammation markers. Recent studies have suggested that SNPs located in gene-encoding microRNAs (miRNAs) affect various aspects of diseases by regulating the expression or activity of miRNAs...
December 7, 2016: Clinical Genetics
https://www.readbyqxmd.com/read/27924974/mir-155-regulates-high-glucose-induced-cardiac-fibrosis-via-the-tgf-%C3%AE-signaling-pathway
#4
Dong Zhang, Yongchun Cui, Bin Li, Xiaokang Luo, Bo Li, Yue Tang
Cardiac fibrosis, as a pathological process, plays an important role in various cardiac diseases. microRNA-155 (miR-155) is one of the most important miRNAs, and previous studies have shown that it is a regulatory factor in various fibrotic diseases. However, the mechanism by which miR-155 affects myocardial fibrosis remains unclear. In this study, we aim to establish the biological function of miR-155 in myocardial fibrosis induced by diabetes in mice. We used normal C57BL/6 wild type (WT) and miR-155 knockout (KO) mice to establish the diabetic model by intraperitoneal injection of streptozotocin, and we utilized echocardiography to evaluate the cardiac function at 30 and 60 days post-modeling...
December 7, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27924862/mesenchymal-stem-cell-transplantation-can-restore-lupus-disease-associated-mirna-expression-and-th1-th2-ratios-in-a-murine-model-of-sle
#5
Eun Wha Choi, MinJae Lee, Ji Woo Song, Il Seob Shin, Sung Joo Kim
C3.MRL-Fas(lpr)/J mice spontaneously develop high titers of anti-dsDNA, mild glomerular nephritis, and severe lymphoproliferation symptoms. This study aimed to compare the effects of long-term serial administration of human adipose tissue-derived mesenchymal stem cells (ASCs), and cyclophosphamide treatment in C3.MRL-Fas(lpr)/J mice using a murine SLE model. C3.MRL-Fas(lpr)/J mice were divided into saline (C), cyclophosphamide (Y), and ASC (H) treatment groups. Background-matched control C3H mice treated with saline (N) were also compared...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27924640/the-association-of-circulating-mir-30a-mir-29-and-mir-133-with-white-coat-hypertension
#6
Yu-Qing Huang, Cheng Huang, Ji-Yan Chen, Jie Li, Ying-Qing Feng
AIM: The aim of the present study was to investigate the association of circulating miRNAs with white-coat hypertension (WCH) and further analyze whether miRNAs could be as potential biomarkers for WCH. METHOD: Quantitative reverse transcriptase PCR (qRT-PCR) was used to evaluate the expression of selected miRNAs. The area under the receiver-operating characteristic curve was used to evaluate diagnostic accuracy. RESULTS: MiR-30a yielded an AUC of 0...
December 7, 2016: Biomarkers in Medicine
https://www.readbyqxmd.com/read/27924512/computational-analysis-reveals-microrna-mrna-regulatory-network-in-esophageal-squamous-cell-carcinoma
#7
Jie Zhao, Bi-Cheng Zhang, Li-Fang Yu, Wei-Xing Wang, Yong Zhao, Zhi-Guo Rao
MicroRNAs (miRNAs) are known to regulate post-transcriptional gene expression. They are involved in carcinogenesis and tumor progression. The aim of this study was to explore the microRNA-mRNA regulatory network in esophageal squamous cell carcinoma (ESCC) using comprehensive computational approaches. In this study we have selected a total of 11 miRNAs from one previously reported study in ESCC. The mRNA targets of these miRNAs were predicted using various algorithms. The expression profiles of these mRNA targets were identified on DNA microarray experiment dataset across ESCC tissue samples...
December 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/27924503/mir-206-inhibits-renal-cell-cancer-growth-by-targeting-gak
#8
Chao Wei, Shen Wang, Zhang-Qun Ye, Zhi-Qiang Chen
Renal cell cancer (RCC) remains one of the most lethal types of cancer in adults. MicroRNAs (miRNAs) play key roles in the pathogenesis of RCC. The role of miR-206 in RCC has not been fully understood. The purpose of this study was to examine the role of miR-206 in the regulation of proliferation and metastasis of RCC and the possible mechanism. miR-206 expression was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in RCC cell lines (786-O and OS-RC-2 cells) and clinical samples...
December 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/27924491/single-molecule-fluorescence-energy-transfer-assays-for-the-characterization-of-reaction-pathways-of-mirna-argonaute-complex
#9
Myung Hyun Jo, Sungchul Hohng
Argonaute proteins are key components of the microRNA-induced silencing complexes (miRISCs) that mediate the posttranscriptional gene silencing of microRNAs and small interfering RNA (siRNAs). The complex reaction mechanism of miRISC is expected to be characterized by tracing the reaction pathways of miRISC at the single-molecule level in real time. In this chapter, we describe single-molecule fluorescence resonance energy transfer (FRET) assays to observe the target binding and reaction pathways of miRISC composed of a recombinant Argonaute and a small RNA...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924488/elucidating-mechanisms-of-molecular-recognition-between-human-argonaute-and-mirna-using-computational-approaches
#10
Hanlun Jiang, Lizhe Zhu, Amélie Héliou, Xin Gao, Julie Bernauer, Xuhui Huang
MicroRNA (miRNA) and Argonaute (AGO) protein together form the RNA-induced silencing complex (RISC) that plays an essential role in the regulation of gene expression. Elucidating the underlying mechanism of AGO-miRNA recognition is thus of great importance not only for the in-depth understanding of miRNA function but also for inspiring new drugs targeting miRNAs. In this chapter we introduce a combined computational approach of molecular dynamics (MD) simulations, Markov state models (MSMs), and protein-RNA docking to investigate AGO-miRNA recognition...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924487/antagonists-of-the-mirna-argonaute-2-protein-complex-anti-mir-agos
#11
Marco F Schmidt, Oliver Korb, Chris Abell
microRNAs (miRNAs) have been identified as high-value drug targets. A widely applied strategy in miRNA inhibition is the use of antisense agents. However, it has been shown that oligonucleotides are poorly cell permeable because of their complex chemical structure and due to their negatively charged backbone. Consequently, the general application of oligonucleotides in therapy is limited. Since miRNAs' functions are executed exclusively by the Argonaute 2 protein, we therefore describe a protocol for the design of a novel miRNA inhibitor class: antagonists of the miRNA-Argonaute 2 protein complex, so-called anti-miR-AGOs, that not only block the crucial binding site of the target miRNA but also bind to the protein's active site...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924485/small-molecules-targeting-the-mirna-binding-domain-of-argonaute-2-from-computer-aided-molecular-design-to-rna-immunoprecipitation
#12
Teresa Bellissimo, Silvia Masciarelli, Elena Poser, Ilaria Genovese, Alberto Del Rio, Gianni Colotti, Francesco Fazi
The development of small-molecule-based target therapy design for human disease and cancer is object of growing attention. Recently, specific microRNA (miRNA) mimicking compounds able to bind the miRNA-binding domain of Argonaute 2 protein (AGO2) to inhibit miRNA loading and its functional activity were described. Computer-aided molecular design techniques and RNA immunoprecipitation represent suitable approaches to identify and experimentally determine if a compound is able to impair the loading of miRNAs on AGO2 protein...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924484/peptide-based-inhibition-of-mirna-guided-gene-silencing
#13
Johannes Danner, Balagopal Pai, Ludwig Wankerl, Gunter Meister
MicroRNAs (miRNAs) are a large class of small noncoding RNAs that regulate the expression of distinct target mRNAs. miRNAs are incorporated into Argonaute (AGO) proteins and guide them to their target mRNAs. Subsequently, AGO proteins recruit a member of the glycine-tryptophan-rich (GW) protein family by direct protein-protein interaction. GW proteins coordinate all downstream processes leading to robust and efficient gene silencing. A short peptide of GW proteins comprising the AGO interaction motif can be used to biochemically isolate endogenous AGO protein complexes...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924483/rapid-generation-of-mirna-inhibitor-leads-by-bioinformatics-and-efficient-high-throughput-screening-methods
#14
Christopher L Haga, Sai Pradeep Velagapudi, Jessica L Childs-Disney, Jacqueline Strivelli, Matthew D Disney, Donald G Phinney
The discovery of microRNAs (miRNAs) has opened an entire new avenue for drug development. These short (15-22 nucleotides) noncoding RNAs, which function in RNA silencing and posttranscriptional regulation of gene expression, have been shown to critically affect numerous pathways in both development and disease progression. Current miRNA drug development focuses on either reintroducing the miRNA into cells through the use of a miRNA mimic or inhibiting its function via use of a synthetic antagomir. Although these methods have shown some success as therapeutics, they face challenges particularly with regard to cellular uptake and for use as systemic reagents...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924482/identification-of-small-molecule-modulators-of-microrna-by-library-screening
#15
Zhangang Xiao, Yangchao Chen
MicroRNAs (miRNAs) function as oncogenes or tumor suppressors and are dysregulated in cancer. miRNAs therefore represent promising therapeutic targets for cancer. Small molecules that could modulate the expression of miRNAs would thus have potential as anticancer agents. Library screening of small molecules targeting miRNAs is a useful technology platform for anticancer drug development. Here, we describe a hepatocellular carcinoma (HCC) cell-based luciferase reporter system which could be used to screen for small molecule modulators of tumor suppressor microRNA-34a...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924481/machine-learning-approaches-toward-building-predictive-models-for-small-molecule-modulators-of-mirna-and-its-utility-in-virtual-screening-of-molecular-databases
#16
Vinita Periwal, Vinod Scaria
The ubiquitous role of microRNAs (miRNAs) in a number of pathological processes has suggested that they could act as potential drug targets. RNA-binding small molecules offer an attractive means for modulating miRNA function. The availability of bioassay data sets for a variety of biological assays and molecules in public domain provides a new opportunity toward utilizing them to create models and further utilize them for in silico virtual screening approaches to prioritize or assign potential functions for small molecules...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924480/design-of-multimodal-small-molecules-targeting-mirnas-biogenesis-synthesis-and-in-vitro-evaluation
#17
Duc D Vo, Maria Duca
microRNAs (miRNAs) are emerging as novel biological targets for medicinal chemists to develop chemical tools for intracellular regulation. In this context, the discovery of small-molecule drugs targeting specific miRNAs and modulating their production or function represents a very promising approach that could be further developed for targeted therapy in miRNA-related pathologies. Here, we describe the design of multimodal small molecules as RNA ligands targeting DICER-mediated miRNA maturation. The synthesis and the biochemical evaluation as ligands of stem-loop-structured precursor microRNAs (pre-miRNAs) are reported...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924479/assessing-the-off-target-effects-of-mirna-inhibitors-on-innate-immune-toll-like-receptors
#18
Geneviève Pépin, Jonathan Ferrand, Michael P Gantier
MicroRNAs (miRNAs) are involved in most cellular processes and are deregulated in several diseases. Antisense miRNA oligonucleotides (AMOs) therefore present novel therapeutic opportunities. Currently, in vivo delivery of AMOs often relies on high doses of nucleic acids, with nonspecific uptake by most tissues. Critically, AMOs accumulate in phagocytic cells where they can interfere with immune functions, such as the activation of Toll-Like Receptors (TLRs). In this chapter, we describe a method to assess the possible off-target effects of AMOs on TLR7, 8, and 9 sensing...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924478/evaluating-synergistic-effects-of-mir-34a-mimics-in-combination-with-other-therapeutic-agents-in-cultured-non-small-cell-lung-cancer-cells
#19
Jane Zhao, Andreas G Bader
Tumor suppressor miRNAs such as miR-34a inhibit tumor growth by simultaneously regulating the expression of multiple important oncogenes across multiple oncogenic pathways and, therefore, provide a strong rationale for developing therapeutic miRNA mimics in combination with other therapeutic cancer agents to augment drug sensitivity. Here, we describe the experimental approach for evaluating miRNA and drug combinations using the "fixed ratio" method in cultured non-small cell lung cancer cells.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924477/assessing-anti-mir-pharmacology-with-mirna-polysome-shift-assay
#20
John R Androsavich
Target engagement measurements are critical for evaluating developmental drug candidates and their pharmacological activity. microRNA (miRNA) Polysome Shift Assay enables measurement of anti-miR drug target engagement (i.e. extent of miRNA inhibition) without the need to pre-identify or pre-validate downstream miRNA-regulated genes. This makes it useful for assessing anti-miR activity in target tissues or cells where biology of the inhibited miRNAs may not be well understood. In addition, miRNA Polysome Shift Assay can be multiplexed to assess inhibition of multiple miRNAs by a single anti-miR, thus guiding drug optimization for enhancing or avoiding these activities as desired...
2017: Methods in Molecular Biology
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