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https://www.readbyqxmd.com/read/28344040/m-6-a-demethylase-alkbh5-maintains-tumorigenicity-of-glioblastoma-stem-like-cells-by-sustaining-foxm1-expression-and-cell-proliferation-program
#1
Sicong Zhang, Boxuan Simen Zhao, Aidong Zhou, Kangyu Lin, Shaoping Zheng, Zhike Lu, Yaohui Chen, Erik P Sulman, Keping Xie, Oliver Bögler, Sadhan Majumder, Chuan He, Suyun Huang
The dynamic and reversible N(6)-methyladenosine (m(6)A) RNA modification installed and erased by N(6)-methyltransferases and demethylases regulates gene expression and cell fate. We show that the m(6)A demethylase ALKBH5 is highly expressed in glioblastoma stem-like cells (GSCs). Silencing ALKBH5 suppresses the proliferation of patient-derived GSCs. Integrated transcriptome and m(6)A-seq analyses revealed altered expression of certain ALKBH5 target genes, including the transcription factor FOXM1. ALKBH5 demethylates FOXM1 nascent transcripts, leading to enhanced FOXM1 expression...
March 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28342449/a-systematic-review-and-meta-analysis-of-the-association-between-long-non-coding-rna-polymorphisms-and-cancer-risk
#2
REVIEW
Zhi Lv, Qian Xu, Yuan Yuan
It has been suggested that long non-coding RNA (lncRNA) gene polymorphisms are associated with cancer risk. In this article, we conducted a systematic review related to studies on the association between lncRNA single-nucleotide polymorphisms (SNPs) and the overall risk of cancer. A total 17 SNPs in four common lncRNA genes were included in the meta-analysis. In the lncRNA H19, the rs2735971 A/G, rs2839698C/T, and rs3024270 G/C polymorphisms, but not rs217727C/T, were correlated with overall cancer risk. The results also suggested that other SNPs were correlated with overall cancer risk, namely, two in HOTAIR (HOX transcript antisense RNA: rs920778C/T and rs7958904 G/C) and two in PRNCR1 (rs1016343C/T and rs16901946 A/G)...
January 2017: Mutation Research
https://www.readbyqxmd.com/read/28342055/the-analysis-of-lncrna-hotair-rs12826786-c-t-polymorphism-and-gastric-cancer-susceptibility-in-a-turkish-population-lack-of-any-association-in-a-hospital-based-case-control-study
#3
Y Ülger, E Dadaş, B Yalinbaş Kaya, A T Sümbül, A Genç, S Bayram
BACKGROUND: The HOX transcript antisense intergenic RNA (HOTAIR), a well-known long noncoding RNA (lncRNA), has been widely identified to participate in pathogenesis of multiple cancers. An aberrant up-regulation and biological functions have been observed in gastric cancer (GC). A common single nucleotide polymorphism (SNP) (rs12826786 C>T) at the HOTAIR has been reported to influence HOTAIR expression, but its association with GC has yet to be investigated in Turkish population. AIM: The aim of the present study was to investigate whether HOTAIR rs12826786 C>T polymorphism could be involved in the risk of GC susceptibility in Turkish population...
March 24, 2017: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/28340355/the-human-immunodeficiency-virus-1-asp-rna-promotes-viral-latency-by-recruiting-the-polycomb-repressor-complex-2-and-promoting-nucleosome-assembly
#4
Juan C Zapata, Federica Campilongo, Robert A Barclay, Catherine DeMarino, Maria D Iglesias-Ussel, Fatah Kashanchi, Fabio Romerio
Various epigenetic marks at the HIV-1 5'LTR suppress proviral expression and promote latency. Cellular antisense transcripts known as long noncoding RNAs (lncRNAs) recruit the polycomb repressor complex 2 (PRC2) to gene promoters, which catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3), thus promoting nucleosome assembly and suppressing gene expression. We found that an HIV-1 antisense transcript expressed from the 3'LTR and encoding the antisense protein ASP promotes proviral latency. Expression of ASP RNA reduced HIV-1 replication in Jurkat cells...
March 21, 2017: Virology
https://www.readbyqxmd.com/read/28339741/shear-stress-regulated-mir-27b-controls-pericyte-recruitment-by-repressing-sema6a-and-sema6d
#5
Shemsi Demolli, Anuradha Doddaballapur, Kavi Devraj, Konstantin Stark, Yosif Manavski, Annekathrin Eckart, Christoph Zehendner, Tina Lucas, Thomas Korff, Markus Hecker, Steffen Massberg, Stefan Liebner, David Kaluza, Reinier A Boon, Stefanie Dimmeler
Aims: Vessel maturation involves the recruitment of mural cells such as pericytes and smooth muscle cells. Laminar shear stress is a major trigger for vessel maturation, but the molecular mechanisms by which shear stress affects recruitment of pericytes are unclear. MicroRNAs (miRs) are small non-coding RNAs, which post-transcriptionally control gene expression. The aim of the present study was to unveil the mechanism by which shear stress-regulated microRNAs contribute to vessel maturation...
February 23, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28334866/c9orf72-and-rab7l1-regulate-vesicle-trafficking-in-amyotrophic-lateral-sclerosis-and-frontotemporal-dementia
#6
Yoshitsugu Aoki, Raquel Manzano, Yi Lee, Ruxandra Dafinca, Misako Aoki, Andrew G L Douglas, Miguel A Varela, Chaitra Sathyaprakash, Jakub Scaber, Paola Barbagallo, Pieter Vader, Imre Mäger, Kariem Ezzat, Martin R Turner, Naoki Ito, Samanta Gasco, Norihiko Ohbayashi, Samir El Andaloussi, Shin'ichi Takeda, Mitsunori Fukuda, Kevin Talbot, Matthew J A Wood
A non-coding hexanucleotide repeat expansion in intron 1 of the C9orf72 gene is the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD), however, the precise molecular mechanism by which the C9orf72 hexanucleotide repeat expansion directs C9ALS/FTD pathogenesis remains unclear. Here, we report a novel disease mechanism arising due to the interaction of C9ORF72 with the RAB7L1 GTPase to regulate vesicle trafficking. Endogenous interaction between C9ORF72 and RAB7L1 was confirmed in human SH-SY5Y neuroblastoma cells...
February 23, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334849/icf-specific-dnmt3b-dysfunction-interferes-with-intragenic-regulation-of-mrna-transcription-and-alternative-splicing
#7
Sole Gatto, Miriam Gagliardi, Monica Franzese, Sylwia Leppert, Mariarosaria Papa, Marco Cammisa, Giacomo Grillo, Guillame Velasco, Claire Francastel, Shir Toubiana, Maurizio D'Esposito, Claudia Angelini, Maria R Matarazzo
Hypomorphic mutations in DNA-methyltransferase DNMT3B cause majority of the rare disorder Immunodeficiency, Centromere instability and Facial anomalies syndrome cases (ICF1). By unspecified mechanisms, mutant-DNMT3B interferes with lymphoid-specific pathways resulting in immune response defects. Interestingly, recent findings report that DNMT3B shapes intragenic CpG-methylation of highly-transcribed genes. However, how the DNMT3B-dependent epigenetic network modulates transcription and whether ICF1-specific mutations impair this process remains unknown...
March 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334800/optimization-of-a-novel-biophysical-model-using-large-scale-in-vivo-antisense-hybridization-data-displays-improved-prediction-capabilities-of-structurally-accessible-rna-regions
#8
Jorge Vazquez-Anderson, Mia K Mihailovic, Kevin C Baldridge, Kristofer G Reyes, Katie Haning, Seung Hee Cho, Paul Amador, Warren B Powell, Lydia M Contreras
Current approaches to design efficient antisense RNAs (asRNAs) rely primarily on a thermodynamic understanding of RNA-RNA interactions. However, these approaches depend on structure predictions and have limited accuracy, arguably due to overlooking important cellular environment factors. In this work, we develop a biophysical model to describe asRNA-RNA hybridization that incorporates in vivo factors using large-scale experimental hybridization data for three model RNAs: a group I intron, CsrB and a tRNA. A unique element of our model is the estimation of the availability of the target region to interact with a given asRNA using a differential entropic consideration of suboptimal structures...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334721/microrna-9-inhibits-nlrp3-inflammasome-activation-in-human-atherosclerosis-inflammation-cell-models-through-the-jak1-stat-signaling-pathway
#9
Yue Wang, Zhihua Han, Yuqi Fan, Junfeng Zhang, Kan Chen, Lin Gao, Huasu Zeng, Jiatian Cao, Changqian Wang
BACKGROUND/AIMS: MicroRNA-9 (miR-9) is involved in inflammatory reaction in atherosclerosis; however, its function and regulatory mechanisms remain unclear. We aimed to uncover the exact roles of miR-9 and downstream signaling pathways using in vitro human atherosclerosis models. METHODS: We used oxidized low-density lipoprotein (oxLDL)-stimulated human THP-1 derived macrophages, oxLDL-stimulated human primary peripheral blood monocytes and lipopolysaccharides (LPS) or Alum-stimulated human THP-1 derived macrophages as in vitro atherosclerosis inflammation models...
March 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28331090/hili-inhibits-hiv-replication-in-activated-t-cells
#10
B Matija Peterlin, Pingyang Liu, Xiaoyun Wang, Daniele Cary, Wei Shao, Marie Leoz, Tian Hong, Tao Pan, Koh Fujinaga
Piwil proteins restrict the replication of mobile genetic elements in the germline. They are also expressed in many transformed cell lines. In this report, we discovered that the human piwil 2 (hili) can also inhibit HIV replication, especially in activated CD4+ T cells that are the preferred target cells for this virus in the infected host. Although resting cells did not express hili, it was rapidly induced following T cell activation. In these cells and transformed cell lines, depletion of hili increased levels of viral proteins and new viral particles...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28330877/k-channel-modulatory-subunits-kchip-and-dpp-participate-in-kv4-mediated-mechanical-pain-control
#11
Yen-Ling Kuo, Jen-Kun Cheng, Wen-Hsien Hou, Yu-Cheng Chang, Po-Hao Du, Jhao-Jun Jian, Ruey-Horng Rau, Jung-Hui Yang, Cheng-Chang Lien, Meei-Ling Tsaur
The K(+) channel pore-forming subunit Kv4.3 is expressed in a subset of non-peptidergic nociceptors within the dorsal root ganglion (DRG), and knockdown of Kv4.3 selectively induces mechanical hypersensitivity, a major symptom of neuropathic pain. K(+) channel modulatory subunits KChIP1, KChIP2 and DPP10 are coexpressed in Kv4.3(+) DRG neurons, but whether they participate in Kv4.3-mediated pain control is unknown. Here, we show the existence of a Kv4.3/KChIP1/KChIP2/DPP10 complex (abbreviated as the Kv4 complex) in the endoplasmic reticulum and cell surface of DRG neurons...
March 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28329241/lipoprotein-a-the-revenant
#12
Baris Gencer, Florian Kronenberg, Erik S Stroes, François Mach
In the mid-1990s, the days of lipoprotein(a) [Lp(a)] were numbered and many people would not have placed a bet on this lipid particle making it to the next century. However, genetic studies brought Lp(a) back to the front-stage after a Mendelian randomization approach used for the first time provided strong support for a causal role of high Lp(a) concentrations in cardiovascular disease and later also for aortic valve stenosis. This encouraged the use of therapeutic interventions to lower Lp(a) as well numerous drug developments, although these approaches mainly targeted LDL cholesterol, while the Lp(a)-lowering effect was only a 'side-effect'...
February 17, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28325760/neisseria-meningitidis-uses-sibling-small-regulatory-rnas-to-switch-from-cataplerotic-to-anaplerotic-metabolism
#13
Yvonne Pannekoek, Robert A G Huis In 't Veld, Kim Schipper, Sandra Bovenkerk, Gertjan Kramer, Matthijs C Brouwer, Diederik van de Beek, Dave Speijer, Arie van der Ende
Neisseria meningitidis (the meningococcus) is primarily a commensal of the human oropharynx that sporadically causes septicemia and meningitis. Meningococci adapt to diverse local host conditions differing in nutrient supply, like the nasopharynx, blood, and cerebrospinal fluid, by changing metabolism and protein repertoire. However, regulatory transcription factors and two-component systems in meningococci involved in adaptation to local nutrient variations are limited. We identified novel sibling small regulatory RNAs ( Neisseriametabolic switch regulators [NmsRs]) regulating switches between cataplerotic and anaplerotic metabolism in this pathogen...
March 21, 2017: MBio
https://www.readbyqxmd.com/read/28325303/inhibition-of-egf-uptake-by-nephrotoxic-antisense-drugs-in%C3%A2-vitro-and-implications-for-preclinical-safety-profiling
#14
Annie Moisan, Marcel Gubler, Jitao David Zhang, Yann Tessier, Kamille Dumong Erichsen, Sabine Sewing, Régine Gérard, Blandine Avignon, Sylwia Huber, Fethallah Benmansour, Xing Chen, Roberto Villaseñor, Annamaria Braendli-Baiocco, Matthias Festag, Andreas Maunz, Thomas Singer, Franz Schuler, Adrian B Roth
Antisense oligonucleotide (AON) therapeutics offer new avenues to pursue clinically relevant targets inaccessible with other technologies. Advances in improving AON affinity and stability by incorporation of high affinity nucleotides, such as locked nucleic acids (LNA), have sometimes been stifled by safety liabilities related to their accumulation in the kidney tubule. In an attempt to predict and understand the mechanisms of LNA-AON-induced renal tubular toxicity, we established human cell models that recapitulate in vivo behavior of pre-clinically and clinically unfavorable LNA-AON drug candidates...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28325281/systemic-antisense-therapeutics-for-dystrophin-and-myostatin-exon-splice-modulation-improve-muscle-pathology-of-adult-mdx-mice
#15
Ngoc Lu-Nguyen, Alberto Malerba, Linda Popplewell, Fred Schnell, Gunnar Hanson, George Dickson
Antisense-mediated exon skipping is a promising approach for the treatment of Duchenne muscular dystrophy (DMD), a rare life-threatening genetic disease due to dystrophin deficiency. Such an approach can restore the disrupted reading frame of dystrophin pre-mRNA, generating a truncated form of the protein. Alternatively, antisense therapy can be used to induce destructive exon skipping of myostatin pre-mRNA, knocking down myostatin expression to enhance muscle strength and reduce fibrosis. We have reported previously that intramuscular or intraperitoneal antisense administration inducing dual exon skipping of dystrophin and myostatin pre-mRNAs was beneficial in mdx mice, a mouse model of DMD, although therapeutic effects were muscle type restricted, possibly due to the delivery routes used...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28323030/antisense-lncrna-foxc2-as1-promotes-doxorubicin-resistance-in-osteosarcoma-by-increasing-the-expression-of-foxc2
#16
Zhang Chun-Lin, Zhu Kun-Peng, Ma Xiao-Long
Recent efforts have revealed that numerous natural antisense lncRNAs play a crucial role in the regulation of cancer biology. Here, based on our previous study, we further identified that the lncRNA FOXC2-AS1 and its antisense transcript FOXC2 were positively up-regulated in doxorubicin-resistant osteosarcoma cell lines and tissues, correlate with poor prognosis and promote doxorubicin resistance in osteosarcoma cells in vitro and in vivo. In addition, FOXC2-AS1 and FOXC2 are mainly located in the cytoplasm and form an RNA-RNA double-stranded structure in the overlapping region, which is necessary for FOXC2-AS1 to regulate the expression of FOXC2 at both the transcription and post-transcription levels...
March 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28317029/listeriomics-an-interactive-web-platform-for-systems-biology-of-listeria
#17
Christophe Bécavin, Mikael Koutero, Nicolas Tchitchek, Franck Cerutti, Pierre Lechat, Nicolas Maillet, Claire Hoede, Hélène Chiapello, Christine Gaspin, Pascale Cossart
As for many model organisms, the amount of Listeria omics data produced has recently increased exponentially. There are now >80 published complete Listeria genomes, around 350 different transcriptomic data sets, and 25 proteomic data sets available. The analysis of these data sets through a systems biology approach and the generation of tools for biologists to browse these various data are a challenge for bioinformaticians. We have developed a web-based platform, named Listeriomics, that integrates different tools for omics data analyses, i...
March 2017: MSystems
https://www.readbyqxmd.com/read/28315297/paxillin-genes-and-actomyosin-contractility-regulate-myotome-morphogenesis-in-zebrafish
#18
Andrew E Jacob, Jeffrey D Amack, Christopher E Turner
Paxillin (Pxn) is a key adapter protein and signaling regulator at sites of cell-extracellular matrix (ECM) adhesion. Here, we investigated the role of Pxn during vertebrate development using the zebrafish embryo as a model system. We have characterized two Pxn genes, pxna and pxnb, in zebrafish that are maternally supplied and expressed in multiple tissues. Gene editing and antisense gene knockdown approaches were used to uncover Pxn functions during zebrafish development. While mutation of either pxna or pxnb alone did not cause gross embryonic phenotypes, double mutants lacking maternally supplied pxna or pxnb displayed defects in cardiovascular, axial, and skeletal muscle development...
March 14, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28314879/a-study-on-associations-of-single-nucleotide-polymorphisms-within-h19-and-hox-transcript-antisense-rna-hotair-with-genetic-susceptibility-to-rheumatoid-arthritis-in-a-chinese-population
#19
Jian-Zhe Zhou, Jing-Jing Li, Dong-Jin Hua, Si-Chao Huang, Qing-Qing Sun, Hua Huang, Xia-Fei Xin, Han Cen
OBJECTIVE: The purpose of our study was to examine whether the H19 rs2839698, rs217727, and HOX transcript antisense RNA (HOTAIR) rs12826786 polymorphisms were associated with genetic susceptibility to rheumatoid arthritis (RA) in a Chinese population. METHODS: A total of 777 participants were enrolled in this study, including 328 RA patients and 449 healthy controls. The H19 rs2839698, rs217727, and HOTAIR rs12826786 polymorphisms were detected by the ligase detection reaction-polymerase chain reaction (LDR-PCR) technology...
March 17, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28306605/hyperalgesic-priming-type-ii-induced-by-repeated-opioid-exposure-maintenance-mechanisms
#20
Dioneia Araldi, Luiz F Ferrari, Jon D Levine
We previously developed a model of opioid-induced neuroplasticity in the peripheral terminal of the nociceptor that could contribute to opioid-induced hyperalgesia, type II hyperalgesic priming. Repeated administration of mu-opioid receptor (MOR) agonists, such as DAMGO, at the peripheral terminal of the nociceptor, induces long-lasting plasticity expressed, prototypically as opioid-induced hyperalgesia and prolongation of prostaglandin-E2-induced hyperalgesia. In this study, we evaluated the mechanisms involved in the maintenance of type II priming...
March 14, 2017: Pain
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