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Antisense protein

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https://www.readbyqxmd.com/read/27924487/antagonists-of-the-mirna-argonaute-2-protein-complex-anti-mir-agos
#1
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/27924473/non-nucleotide-modification-of-anti-mirna-oligonucleotides
#2
Kim A Lennox, Christopher A Vakulskas, Mark A Behlke
MicroRNAs (miRNAs) are important modulators of gene expression. Synthetic anti-microRNA oligonucleotides (AMOs, or anti-miRs) are a form of steric-blocking antisense oligonucleotides (ASOs) that inhibit miRNA function through high-affinity binding and subsequent inactivation and/or degradation of the targeted miRNA. AMOs are a primary tool used to empirically determine the biological targets of a miRNA and can also be used therapeutically when overexpression of a miRNA contributes to a disease state. Chemical modification of synthetic AMOs enhance potency by protecting the oligonucleotide from nuclease degradation and by increasing binding affinity to the target miRNA...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27920156/nf%C3%AE%C2%BAb-induced-periostin-activates-integrin-%C3%AE-3-signaling-to-promote-renal-injury-in-gn
#3
Niki Prakoura, Panagiotis Kavvadas, Raphaёl Kormann, Jean-Claude Dussaule, Christos E Chadjichristos, Christos Chatziantoniou
De novo expression in the kidney of periostin, a protein involved in odontogenesis and osteogenesis, has been suggested as a biomarker of renal disease. In this study, we investigated the mechanism(s) of induction and the role of periostin in renal disease. Using a combination of bioinformatics, reporter assay, and chromatin immunoprecipitation analyses, we found that NFκB and other proinflammatory transcription factors induce periostin expression in vitro and that binding of these factors on the periostin promoter is enriched in glomeruli during experimental GN...
December 5, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27919344/jcl-roundtable-risk-evaluation-and-mitigation-strategy
#4
REVIEW
W Virgil Brown, Dean A Bramlet, Joyce L Ross, James A Underberg
Many factors enter into the decision by the Food and Drug Administration (FDA) to approve a new drug for use by physicians and other health care providers in treating diseases. Initially, the FDA authority was restricted to issues of safety and only later did the documentation of efficacy become part of the review process required for approval. However, all drugs have the potential for causing harm at some dose level to all and at lower doses in certain patients with vulnerability to the particular pharmacology of the agent...
November 2016: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/27916649/new-horizons-for-cystic-fibrosis-treatment
#5
REVIEW
Isabelle Fajac, Kris De Boeck
Cystic fibrosis is an inherited multi-system disease associated with chronic lung infection, malabsorption, salt loss syndromes, male infertility and leading to numerous comorbidities. The landscape in cystic fibrosis care has changed markedly with currently more adult patients than children in many countries. Over 2000 different mutations in theCFTRgene have been reported and the majority are extremely rare. Understanding howCFTRmutations translate to disturbed synthesis or function of the CFTR protein has opened the way to 'personalized' treatments to correct the basic defect...
December 1, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27916230/retraction-notice-to-introduction-of-antisense-oligonucleotides-to-heat-shock-protein-47-prevents-pulmonary-fibrosis-in-lipopolysaccharide-induced-pneumopathy-of-the-rat-eur-j-pharmacol-564-1-3-2007-174-180
#6
Satoshi Hagiwara, Hideo Iwasaka, Shigekiyo Matsumoto, Takayuki Noguchi
No abstract text is available yet for this article.
December 5, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27912212/knockdown-of-inhibitory-guanine-nucleotide-binding-protein-gi%C3%AE-2-by-antisense-oligodeoxynucleotides-attenuates-the-development-of-hypertension-and-tachycardia-in-spontaneously-hypertensive-rats
#7
Yousra Ali El-Basyuni, Yuan Li, Madhu B Anand-Srivastava
BACKGROUND: We previously showed that the levels of both Giα-2 and Giα-3 proteins were augmented in spontaneously hypertensive rats (SHRs) before the onset of hypertension. In addition, intraperitoneal injection of pertussis toxin, which inactivates both Giα proteins, prevented the development of hypertension in SHRs. The aim of the present study was to determine the specific contributions of Giα-2 and Giα-3 proteins to the development of hypertension. METHODS AND RESULTS: Antisense oligodeoxynucleotide of Giα-2 and Giα-3 encapsulated in PEG/DOTAP/DOPE cationic liposomes were administrated intravenously into 3-week-old prehypertensive SHRs and Wistar Kyoto rats, whereas the control Wistar Kyoto rats and SHRs received PBS, empty liposomes, or sense...
October 26, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27907033/normalization-of-patient-identified-plasma-biomarkers-in-smn%C3%AE-7-mice-following-postnatal-smn-restoration
#8
W David Arnold, Sandra Duque, Chitra C Iyer, Phillip Zaworski, Vicki L McGovern, Shannon J Taylor, Katharine M von Herrmann, Dione T Kobayashi, Karen S Chen, Stephen J Kolb, Sergey V Paushkin, Arthur H M Burghes
INTRODUCTION AND OBJECTIVE: Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disorder. SMA is caused by homozygous loss of the SMN1 gene and retention of the SMN2 gene resulting in reduced levels of full length SMN protein that are insufficient for motor neuron function. Various treatments that restore levels of SMN are currently in clinical trials and biomarkers are needed to determine the response to treatment. Here, we sought to investigate in SMA mice a set of plasma analytes, previously identified in patients with SMA to correlate with motor function...
2016: PloS One
https://www.readbyqxmd.com/read/27906431/overexpression-of-microrna-365-inhibits-breast-cancer-cell-growth-and-chemo-resistance-through-galnt4
#9
J Zhang, Z Zhang, Q Wang, X-J Xing, Y Zhao
OBJECTIVE: A role of microRNA-365 (miR-365) in the carcinogenesis of breast cancer remains undetermined. In the current study, we addressed this question. PATIENTS AND METHODS: We examined the levels of miR-365 in breast cancer tissue, compared to the paired adjacent non-tumor breast tissue from the patients. We also examined the effects of miR-365 modification on the breast cancer growth and sensitivity to Fluorouracil, as well as the underlying mechanisms. RESULTS: The miR-365 levels in breast cancer tissue were significantly lower than those in control normal breast tissues...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27904776/microrna-195-suppresses-colorectal-cancer-cells-proliferation-via-targeting-fgf2-and-regulating-wnt-%C3%AE-catenin-pathway
#10
Xianxiang Zhang, Ji Xu, Tao Jiang, Guangwei Liu, Dongsheng Wang, Yun Lu
Colorectal cancer (CRC) is a prevalent cancer with high mortality worldwide. This study was aimed to explore the functional effects of microRNA-195 (miR-195) on CRC cells and the underling mechanism involved. quantitative PCR (qPCR) was performed to monitor the expression of miR-195 in CRC tissues and cell lines. SW480 and SW620 cells were transfected with either miR-195 mimic or antisense oligonucleotides (ASO) of miR-195. Then cell viability, cell cycle and the expressions of CyclinB1, CyclinD1 and Cyclin-Dependent Kinase 2 (CDK2) were respectively detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyltetrazolium bromide (MTT), flow cytometry, qPCR and Western blot...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27904706/the-central-role-of-hotair-in-the-malignancy-of-cd44-human-hypopharyngeal-carcinoma-cells
#11
Hongxia Cheng, Xinhua Cui, Ying Guo, Lintao Gu, Yaning Wang, Qirong Wang, Hui Liang
Human hypopharyngeal carcinoma is one of the most common malignant tumors. CD44 could serve as a molecular marker to screen for cancer stem cells (CSCs) in hypopharyngeal cancer. The aim of this study was to identify the role of HOX transcript antisense RNA (HOTAIR) on cell proliferation and invasion in CD44+ FADU cells (human hypopharyngeal carcinoma cells). We also explored the underlying mechanism contributing to HOTAIR's observed effects. CD44+ FADU cells were sorted and purified by flow cytometry and infected with lentivirus stably expressing HOTAIR shRNA...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27899596/chitars-3-1-the-enhanced-chimeric-transcripts-and-rna-seq-database-matched-with-protein-protein-interactions
#12
Alessandro Gorohovski, Somnath Tagore, Vikrant Palande, Assaf Malka, Dorith Raviv-Shay, Milana Frenkel-Morgenstern
Discovery of chimeric RNAs, which are produced by chromosomal translocations as well as the joining of exons from different genes by trans-splicing, has added a new level of complexity to our study and understanding of the transcriptome. The enhanced ChiTaRS-3.1 database (http://chitars.md.biu.ac.il) is designed to make widely accessible a wealth of mined data on chimeric RNAs, with easy-to-use analytical tools built-in. The database comprises 34 922: chimeric transcripts along with 11 714: cancer breakpoints...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27896736/structural-and-functional-annotation-of-long-noncoding-rnas
#13
Martin A Smith, John S Mattick
Protein-coding RNAs represent only a small fraction of the transcriptional output in higher eukaryotes. The remaining RNA species encompass a broad range of molecular functions and regulatory roles, a consequence of the structural polyvalence of RNA polymers. Albeit several classes of small noncoding RNAs are relatively well characterized, the accessibility of affordable high-throughput sequencing is generating a wealth of novel, unannotated transcripts, especially long noncoding RNAs (lncRNAs) that are derived from genomic regions that are antisense, intronic, intergenic, and overlapping protein-coding loci...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27896589/lipid-nanoparticles-loaded-with-an-antisense-oligonucleotide-gapmer-against-bcl-2-for-treatment-of-lung-cancer
#14
Xinwei Cheng, Qibing Liu, Hong Li, Chen Kang, Yang Liu, Tianqi Guo, Ke Shang, Chengyun Yan, Guang Cheng, Robert J Lee
PURPOSE: Bcl-2 is an anti-apoptotic gene that is frequently overexpressed in human cancers. G3139 is an antisense oligonucleotide against bcl-2 that has shown limited efficacy in clinical trials. Here, we report the synthesis of a new antisense oligonucleotide containing additional chemical modifications and its delivery using nanoparticles. METHODS: An oligonucleotide G3139-GAP was synthesized, which has 2'-O-methyl nucleotides at the 5' and 3' ends based on a "gapmer" design...
November 28, 2016: Pharmaceutical Research
https://www.readbyqxmd.com/read/27895744/identification-of-targets-of-mirna-221-and-mirna-222-in-fulvestrant-resistant-breast-cancer
#15
Pengfei Liu, Manna Sun, Wenhua Jiang, Jinkun Zhao, Chunyong Liang, Huilai Zhang
The present study aimed to identify the differentially expressed genes (DEGs) regulated by microRNA (miRNA)-221 and miRNA-222 that are associated with the resistance of breast cancer to fulvestrant. The GSE19777 transcription profile was downloaded from the Gene Expression Omnibus database, and includes data from three samples of antisense miRNA-221-transfected fulvestrant-resistant MCF7-FR breast cancer cells, three samples of antisense miRNA-222-transfected fulvestrant-resistant MCF7-FR cells and three samples of control inhibitor (green fluorescent protein)-treated fulvestrant-resistant MCF7-FR cells...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27892455/selective-suppression-of-antisense-transcription-by-set2-mediated-h3k36-methylation
#16
Swaminathan Venkatesh, Hua Li, Madelaine M Gogol, Jerry L Workman
Maintenance of a regular chromatin structure over the coding regions of genes occurs co-transcriptionally via the 'chromatin resetting' pathway. One of the central players in this pathway is the histone methyltransferase Set2. Here we show that the loss of Set2 in yeast, Saccharomyces cerevisiae, results in transcription initiation of antisense RNAs embedded within body of protein-coding genes. These RNAs are distinct from the previously identified non-coding RNAs and cover 11% of the yeast genome. These RNA species have been named Set2-repressed antisense transcripts (SRATs) since the co-transcriptional addition of the H3K36 methyl mark by Set2 over their start sites results in their suppression...
November 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27890673/functional-validation-of-abhd12-mutations-in-the-neurodegenerative-disease-pharc
#17
Angèle Tingaud-Sequeira, Demetrio Raldúa, Julie Lavie, Guilaine Mathieu, Magali Bordier, Anja Knoll-Gellida, Pierre Rambeau, Isabelle Coupry, Michèle André, Eva Malm, Claes Möller, Sten Andreasson, Nanna D Rendtorff, Lisbeth Tranebjærg, Michel Koenig, Didier Lacombe, Cyril Goizet, Patrick J Babin
ABHD12 mutations have been linked to neurodegenerative PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and early-onset cataract), a rare, progressive, autosomal, recessive disease. Although ABHD12 is suspected to play a role in the lysophosphatidylserine and/or endocannabinoid pathways, its precise functional role(s) leading to PHARC disease had not previously been characterized. Cell and zebrafish models were designed to demonstrate the causal link between an identified new missense mutation p...
November 23, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27889749/contribution-of-p38-mapk-to-the-ameliorating-effect-of-enriched-environment-on-the-cognitive-deficits-induced-by-chronic-cerebral-hypoperfusion
#18
Yu-Wang Li, Qing-Yun Li, Jin-Hua Wang, Xiao-Lin Xu
BACKGROUND/AIMS: An enriched environment (EE) ameliorates learning and memory impairments induced by chronic cerebral hypoperfusion, and the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway exerts both beneficial and deleterious effects on the nervous system during the progression of ischemia. METHODS: The present study investigated whether p38 MAPK participates in the process by which EE exposure ameliorates the cognitive deficits induced by chronic cerebral hypoperfusion...
November 25, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27888605/natural-antisense-transcripts-are-linked-to-the-modulation-of-mitochondrial-function-and-teliospore-dormancy-in-ustilago-maydis
#19
Lauren A Ostrowski, Barry J Saville
The basidiomycete smut fungus Ustilago maydis causes common smut of corn. This disease is spread through the production of teliospores, which are thick-walled dormant structures characterized by low rates of respiration and metabolism. Teliospores are formed when the fungus grows within the plant, and the morphological steps involved in their formation have been described, but the molecular events leading to dormancy are not known. In U. maydis, natural antisense transcripts (NATs) can function to alter gene expression and many NATs have increased levels in the teliospore...
November 26, 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/27888476/histological-detection-of-dynamic-glial-responses-in-the-dysmyelinating-tabby-jimpy-mutant-brain
#20
Masanao Ikeda, M Ibrahim Hossain, Li Zhou, Masao Horie, Kazuhiro Ikenaka, Arata Horii, Hirohide Takebayashi
Oligodendrocytes (OLs) are glial cells that form myelin sheaths surrounding the axons in the central nervous system (CNS). Jimpy (jp) mutant mice are dysmyelinating disease models that show developmental abnormalities in myelinated OLs in the CNS. The causative gene in jp mice is the proteolipid protein (PLP) located on the X chromosome. Mutations in the jp allele result in exon 5 skipping and expression of abnormal PLP containing a C-terminal frame shift. Many lines of evidence suggest that abnormal PLP in OLs results in endoplasmic reticulum (ER) stress and cell death...
November 25, 2016: Anatomical Science International
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