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https://www.readbyqxmd.com/read/28811264/protein-coding-genes-as-hosts-for-noncoding-rna-expression
#1
REVIEW
Vincent Boivin, Gabrielle Deschamps-Francoeur, Michelle S Scott
With the emergence of high-throughput sequence characterization methods and the subsequent improvements in gene annotations, it is becoming increasingly clear that a large proportion of eukaryotic protein-coding genes (as many as 50% in human) serve as host genes for non-coding RNA genes. Amongst the most extensively characterized embedded non-coding RNA genes, small nucleolar RNAs and microRNAs represent abundant families. Encoded individually or clustered, in sense or antisense orientation with respect to their host and independently expressed or dependent on host expression, the genomic characteristics of embedded genes determine their biogenesis and the extent of their relationship with their host gene...
August 12, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28809818/synthesis-of-5-galnac-conjugated-oligonucleotides-a-comparison-of-solid-and-solution-phase-conjugation-strategies
#2
Isaiah Cedillo, Dana Chreng, Elyse Engle, Lijian Chen, Andrew K McPherson, Andrew A Rodriguez
Antisense oligonucleotides (ASOs) conjugated to triantennary N-acetyl galactosamine (GalNAc) ligands represent an emerging approach to antisense therapy. Our current generation of GalNAc-ASO conjugates link the GalNAc to the 5'-terminus of the ASO. The conjugation reaction can be accomplished using solution-phase or solid-phase techniques. Here we show a direct comparison of a solution-phase and a solid-phase conjugation strategy. The solution-phase approach, using amine-pentafluorophenyl (PFP) ester coupling, is higher yielding and gives material of slightly higher purity, but requires several additional unit operations and longer production time...
August 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28807725/the-rnf146-e3-ubiquitin-ligase-is-required-for-the-control-of-wnt-signaling-and-body-pattern-formation-in-xenopus
#3
Xuechen Zhu, Rui Xing, Renbo Tan, Rongyang Dai, Qinghua Tao
The RING finger protein Rnf146 encodes an E3 ubiquitin ligase capable of targeting poly-ADP-ribosylated substrates for proteasomal degradation. Rnf146 has been identified as a critical regulator of Axin1 and thus of Wnt/β-catenin signaling. However its physiological significance in vertebrate embryonic development remains to be demonstrated. In this study, we take advantages of early Xenopus embryos to demonstrate that Rnf146 is essential for embryonic pattern formation. Depletion of zygotic Rnf146 using a translation blocking morpholino oligo (MO) results in anteriorized development and increased expression the anterior marker gene Otx2, consistent the notion that Rnf146 is a positive regulator of Wnt/β-catenin signaling through negatively regulating Axin1 expression...
August 11, 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/28806224/bromodomain-containing-protein-4-activates-voltage-gated-sodium-channel-1-7-transcription-in-dorsal-root-ganglia-neurons-to-mediate-thermal-hyperalgesia-in-rats
#4
Ming-Chun Hsieh, Yu-Cheng Ho, Cheng-Yuan Lai, Hsueh-Hsiao Wang, An-Sheng Lee, Jen-Kun Cheng, Yat-Pang Chau, Hsien-Yu Peng
BACKGROUND: Bromodomain-containing protein 4 binds acetylated promoter histones and promotes transcription; however, the role of bromodomain-containing protein 4 in inflammatory hyperalgesia remains unclear. METHODS: Male Sprague-Dawley rats received hind paw injections of complete Freund's adjuvant to induce hyperalgesia. The dorsal root ganglia were examined to detect changes in bromodomain-containing protein 4 expression and the activation of genes involved in the expression of voltage-gated sodium channel 1...
August 11, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28805496/natural-antisense-transcripts-drive-a-regulatory-cascade-controlling-c-myc-transcription
#5
Sara Napoli, Valentina Piccinelli, Sarah Mapelli, Giuseppina Pisignano, Carlo V Catapano
Cis-natural antisense transcripts (cis-NATs) are long noncoding RNAs transcribed from the opposite strand and overlapping coding and noncoding genes on the sense strand. cis-NATs are widely present in the human genome and can be involved in multiple mechanisms of gene regulation. Here, we describe the presence of cis-NATs in the 3' distal region of the c-MYC locus and investigate their impact on transcriptional regulation of this key oncogene in human cancers. We found that cis-NATs are produced as consequence of the activation of cryptic transcription initiation sites in the 3' distal region downstream of the c-MYC 3'UTR...
August 14, 2017: RNA Biology
https://www.readbyqxmd.com/read/28803729/the-ground-state-and-evolution-of-promoter-region-directionality
#6
Yi Jin, Umut Eser, Kevin Struhl, L Stirling Churchman
Eukaryotic promoter regions are frequently divergently transcribed in vivo, but it is unknown whether the resultant antisense RNAs are a mechanistic by-product of RNA polymerase II (Pol II) transcription or biologically meaningful. Here, we use a functional evolutionary approach that involves nascent transcript mapping in S. cerevisiae strains containing foreign yeast DNA. Promoter regions in foreign environments lose the directionality they have in their native species. Strikingly, fortuitous promoter regions arising in foreign DNA produce equal transcription in both directions, indicating that divergent transcription is a mechanistic feature that does not imply a function for these transcripts...
August 9, 2017: Cell
https://www.readbyqxmd.com/read/28803245/mir-143-5p-deficiency-triggers-emt-and-metastasis-by-targeting-hif-1%C3%AE-in-gallbladder-cancer
#7
Min He, Ming Zhan, Wei Chen, Sunwang Xu, Manmei Long, Hui Shen, Yongheng Shi, Qiang Liu, Man Mohan, Jian Wang
BACKGROUND/AIMS: Early metastasis plays a pivotal role in tumor-caused death in gallbladder cancer (GBC) patients. Increasing evidence suggest that miR-143-5p is an active player involved in cancer metastasis and a potential therapeutic target. However, its role in the development of GBC cells remains unclear. The aim of this study is to reveal the inhibiting effects of miR-143-5p on the proliferation and metastasis in GBC. METHODS: Quantitative real-time PCR were used to investigate miR-143-5p and its target HIF-1α mRNA levels...
August 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28799823/lack-of-qt-prolongation-for-2-o-methoxyethyl-modified-antisense-oligonucleotides-based-on-retrospective-exposure-response-analysis-of-ten-phase-1-dose-escalation-placebo-controlled-studies-in-healthy-subjects
#8
Rosie Z Yu, Rudy Gunawan, Richard S Geary, Steven G Hughes, Scott P Henry, Yanfeng Wang
The potential of QT prolongation of ten 2'-O-methoxyethyl-modified (2'-MOE) antisense oligonucleotides (ASOs) was evaluated retrospectively via exposure/response (ER) analysis using data from Phase 1 clinical studies in healthy subjects. All Phase 1 studies were double-blind, placebo-controlled, single and multiple ascending dose studies designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of the ASOs in healthy subjects. The active doses in these studies ranged from 50 to 450 mg administered by subcutaneous (SC) injection in single and multiple ascending dose cohorts...
August 11, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/28799578/nusinersen-antisense-oligonucleotide-to-increase-smn-protein-production-in-spinal-muscular-atrophy
#9
D M Paton
Patients with spinal muscular atrophy (SMA) have an autosomal recessive disease that limits their ability to produce survival motor neuron (SMN) protein in the CNS resulting in progressive wasting of voluntary muscles. Detailed studies over several years have demonstrated that phosphorothioate and 2'-O-methoxyethyl- modified antisense oligonucleotides (ASOs) targeting the ISS-N1 site increase SMN2 exon 7 inclusion, thus increasing levels of SMN protein in a dose- and time-dependent manner in liver, kidney and skeletal muscle, and CNS tissues only when administered intrathecally...
June 2017: Drugs of Today
https://www.readbyqxmd.com/read/28796573/development-of-exon-skipping-therapies-for-duchenne-muscular-dystrophy-a-critical-review-and-a-perspective-on-the-outstanding-issues
#10
Annemieke Aartsma-Rus, Volker Straub, Robert Hemmings, Manuel Haas, Gabriele Schlosser-Weber, Violeta Stoyanova-Beninska, Eugenio Mercuri, Francesco Muntoni, Bruno Sepodes, Elizabeth Vroom, Pavel Balabanov
Duchenne muscular dystrophy (DMD) is a rare, severe, progressive muscle-wasting disease leading to disability and premature death. Patients lack the muscle membrane-stabilizing protein dystrophin. Antisense oligonucleotide (AON)-mediated exon skipping is a therapeutic approach that aims to induce production of partially functional dystrophins. Recently, an AON targeting exon 51 became the first of its class to be approved by the United States regulators [Food and Drug Administration (FDA)] for the treatment of DMD...
August 10, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/28795449/zebrafish-models-of-orofacial-clefts
#11
REVIEW
Kaylia Duncan, Kusumika Mukherjee, Robert A Cornell, Eric C Liao
Zebrafish is a model organism that affords experimental advantages toward investigating the normal function of genes associated with congenital birth defects. Here we summarize zebrafish studies of genes implicated in orofacial cleft (OFC). The most common use of zebrafish in this context has been to explore the normal function an OFC-associated gene product in craniofacial morphogenesis by inhibiting expression of its zebrafish ortholog. The most frequently deployed method has been to inject embryos with antisense morpholino oligonucleotides targeting the desired transcript...
August 10, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28794451/vitamin-b12-as-a-carrier-of-peptide-nucleic-acid-pna-into-bacterial-cells
#12
Marcin Równicki, Monika Wojciechowska, Aleksandra J Wierzba, Jakub Czarnecki, Dariusz Bartosik, Dorota Gryko, Joanna Trylska
Short modified oligonucleotides targeted at bacterial DNA or RNA could serve as antibacterial agents provided that they are efficiently taken up by bacterial cells. However, the uptake of such oligonucleotides is hindered by the bacterial cell wall. To overcome this problem, oligomers have been attached to cell-penetrating peptides, but the efficiency of delivery remains poor. Thus, we have investigated the ability of vitamin B12 to transport peptide nucleic acid (PNA) oligomers into cells of Escherichia coli and Salmonella Typhimurium...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28792970/targeting-hepatic-heparin-binding-egf-like-growth-factor-hb-egf-induces-anti-hyperlipidemia-leading-to-reduction-of-angiotensin-ii-induced-aneurysm-development
#13
Seonwook Kim, Lihua Yang, Seongu Kim, Richard G Lee, Mark J Graham, Judith A Berliner, Aldons J Lusis, Lei Cai, Ryan E Temel, Debra L Rateri, Sangderk Lee
OBJECTIVE: The upregulated expression of heparin binding EGF-like growth factor (HB-EGF) in the vessel and circulation is associated with risk of cardiovascular disease. In this study, we tested the effects of HB-EGF targeting using HB-EGF-specific antisense oligonucleotide (ASO) on the development of aortic aneurysm in a mouse aneurysm model. APPROACH AND RESULTS: Low-density lipoprotein receptor (LDLR) deficient mice (male, 16 weeks of age) were injected with control and HB-EGF ASOs for 10 weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28791413/knockdown-of-hotair-suppresses-proliferation-and-cell-cycle-progression-in-hepatocellular-carcinoma-cell-by-downregulating-ccnd1-expression
#14
Jia-Jia Zhou, Di Cheng, Xiao-Yu He, Zhe Meng, Wen-Zhu Li, Ru-Fu Chen
The long noncoding RNA, homeobox transcript antisense RNA (Hotair), has been demonstrated to have an important role in regulating various biological processes in various cancers, including hepatocellular carcinoma (HCC). However, the importance of Hotair in HCC proliferation and cell cycle progression remains to be elucidated. In the present study, knockdown of HOTAIR expression by RNA interference inhibited cell proliferation and induced G0/G1 cell cycle arrest in Huh7 hepatocellular carcinoma cells. In addition, the expression levels of CCND1 mRNA and its cyclin D1 protein product were reduced in Huh7 cells following knockdown of HOTAIR...
August 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28791380/knockdown-of-lncrna-hnf1a-as1-inhibits-oncogenic-phenotypes-in-colorectal-carcinoma
#15
Wenyi Zhu, Peipei Zhuang, Wen Song, Shiyu Duan, Qiong Xu, Man Peng, Jun Zhou
Long non-coding RNAs (lncRNAs) have been demonstrated to serve important roles in the development and progression of cancer. Recently HNF1A antisense RNA 1 (HNF1A‑AS1), a lncRNA, has been reported as exhibiting a potential oncogenic role in the development of many types of cancer. However, the expression and the role of HNF1A‑AS1 in colorectal carcinoma (CRC) remains unclear. In the present study, the role of HNF1A‑AS1 in CRC was examined for the first time and its correlation with CRC cell biological behaviors was analyzed...
August 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28790838/downregulation-of-lncrna-sdpr-as-is-associated-with-poor-prognosis-in-renal-cell-carcinoma
#16
Wenjun Ni, Erlin Song, Mancheng Gong, Yongxiang Li, Jie Yao, Ruihua An
Renal cell carcinoma (RCC) is a common type of kidney cancer. Normally, surgical treatment can prolong life, but only for patients with early stage tumors. However, it is difficult for early detection strategies to distinguish between benign and malignant kidney tumors. Therefore, potential biomarkers for early diagnosis and prognosis of RCC are needed. Intriguingly, mounting evidence has demonstrated that many long noncoding RNAs (lncRNAs) are strongly linked to cancers. Indeed, promising RCC-associated lncRNA biomarkers have also been identified...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28790409/plant-organ-evolution-revealed-by-phylotranscriptomics-in-arabidopsis-thaliana
#17
Li Lei, Joshua G Steffen, Edward J Osborne, Christopher Toomajian
The evolution of phenotypes occurs through changes both in protein sequence and gene expression levels. Though much of plant morphological evolution can be explained by changes in gene expression, examining its evolution has challenges. To gain a new perspective on organ evolution in plants, we applied a phylotranscriptomics approach. We combined a phylostratigraphic approach with gene expression based on the strand-specific RNA-seq data from seedling, floral bud, and root of 19 Arabidopsis thaliana accessions to examine the age and sequence divergence of transcriptomes from these organs and how they adapted over time...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28782835/identification-and-functional-analysis-of-a-potential-key-lncrna-involved-in-fat-loss-of-cancer-cachexia
#18
Huiquan Liu, Ting Zhou, Bangyan Wang, Lu Li, Dawei Ye, Shiying Yu
Cancer cachexia is a devastating, multifactorial and irreversible syndrome characterized by skeletal muscle reduction with or without fat loss. Although much attention has been focused on muscle wasting, fat loss may occur earlier and accelerate muscle wasting in cachexia. The cause of 20% of cancer related death makes it urgent to discover molecular mechanisms behind cancer cachexia. Here we applied weighted gene co-expression network analysis(WGCNA) to identify cachexia related gene modules using differentially expressed 3289 genes and 59 long non-coding RNAs based on microarray data of cachectic and non-cachectic subcutaneous adipose tissue...
August 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28782472/canonical-microrna-matching-differs-greatly-across-groups-of-g-protein-coupled-receptor-mrnas
#19
Michael S Parker, Ambikaipakan Balasubramaniam, Floyd R Sallee, Steven L Parker
BACKGROUND: Heptahelical G protein coupled receptors (GPCRs) support numerous sensory and metabolic functions and differ considerably in levels of expression. GPCR protein levels should link to regulation of GPCR mRNAs by microRNAs (miRs), which might significantly depend on numbers, size and GC content of the canonical antisense matches in mRNAs. These parameters of GPCR mRNAs have not been studied in detail. METHODS: Canonical matching profiles of human GPCR mRNAs and miRs were examined using segments of 7-15 nucleotides in windows shifted by one position over the entire microRNA sequence...
August 4, 2017: MicroRNA
https://www.readbyqxmd.com/read/28782268/reprogramming-antagonizes-the-oncogenicity-of-hoxa13-long-noncoding-rna-hottip-axis-in-gastric-cancer-cells
#20
Deng-Chyang Wu, Sophie S W Wang, Chung-Jung Liu, Kenly Wuputra, Kohsuke Kato, Yen-Liang Lee, Ying-Chu Lin, Ming-Ho Tsai, Chia-Chen Ku, Wen-Hsin Lin, Shin-Wei Wang, Shotaro Kishikawa, Michiya Noguchi, Chu-Chieh Wu, Yi-Ting Chen, Chee-Yin Chai, Chen-Lung Steve Lin, Kung-Kai Kuo, Ya-Han Yang, Hiroyuki Miyoshi, Yukio Nakamura, Shigeo Saito, Kyosuke Nagata, Chang-Shen Lin, Kazunari K Yokoyama
Reprogramming of cancer cells into induced pluripotent stem (iPSCs) is a compelling idea for inhibiting oncogenesis, especially through modulation of homeobox proteins in this reprogramming process. We examined the role of various long noncoding RNAs (lncRNAs)-homeobox protein HOXA13 axis on the switching of the oncogenic function of bone morphogenetic protein 7 (BMP7), which is significantly lost in the gastric cancer cell derived iPS-like cells (iPSLCs). BMP promoter activation occurred through the corecruitment of HOXA13, mixed-lineage leukemia 1 lysine N-methyltransferase (MLL1), WD repeat-containing protein 5 (WDR5), and lncRNA HoxA transcript at the distal tip (HOTTIP) to commit the epigenetic changes to the trimethylation of lysine 4 on histone H3 in cancer cells...
August 7, 2017: Stem Cells
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