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Antisense protein

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https://www.readbyqxmd.com/read/28938565/lncrna-afap1-as1-promotes-growth-and-metastasis-of-cholangiocarcinoma-cells
#1
Xiuhui Shi, Hang Zhang, Min Wang, Xiaodong Xu, Yan Zhao, Ruizhi He, Min Zhang, Min Zhou, Xu Li, Feng Peng, Chengjian Shi, Ming Shen, Xin Wang, Xingjun Guo, Renyi Qin
We investigated the role of actin filament associated protein 1 antisense RNA1 (AFAP1-AS1) lncRNA in promoting cholangiocarcinoma (CCA). qRT-PCR analysis of patient samples showed that AFAP1-AS1 expression was higher in CCA tumors than matched adjacent non-tumor tissue. AFAP1-AS1 levels were also higher in CCA cell lines (HuCCT1 and TFK-1) than a normal biliary epithelium cell line (HIBEpic). AFAP1-AS1 knockdown in CCA cell lines using shAFAP1-AS1 reduced cell proliferation and colony formation in CCK-8 and colony formation assays, respectively...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28935773/a-randomized-double-blinded-phase-ii-trial-of-gemcitabine-and-nab-paclitaxel-plus-apatorsen-or-placebo-in-patients-with-metastatic-pancreatic-cancer-the-rainier-trial
#2
Andrew H Ko, Patrick B Murphy, James D Peyton, Dianna L Shipley, Ahmed Al-Hazzouri, Francisco A Rodriguez, Mark S Womack, Henry Q Xiong, David M Waterhouse, Margaret A Tempero, Shuangli Guo, Cassie M Lane, Chris Earwood, Laura M DeBusk, Johanna C Bendell
LESSONS LEARNED: The addition of the heat shock protein 27 (Hsp27)-targeting antisense oligonucleotide, apatorsen, to a standard first-line chemotherapy regimen did not result in improved survival in unselected patients with metastatic pancreatic cancer.Findings from this trial hint at the possible prognostic and predictive value of serum Hsp27 that may warrant further investigation. BACKGROUND: This randomized, double-blinded, phase II trial evaluated the efficacy of gemcitabine/nab-paclitaxel plus either apatorsen, an antisense oligonucleotide targeting heat shock protein 27 (Hsp27) mRNA, or placebo in patients with metastatic pancreatic cancer...
September 21, 2017: Oncologist
https://www.readbyqxmd.com/read/28934489/antisense-oligonucleotides-targeting-translation-inhibitory-elements-in-5-utrs-can-selectively-increase-protein-levels
#3
Xue-Hai Liang, Hong Sun, Wen Shen, Shiyu Wang, Joyee Yao, Michael T Migawa, Huynh-Hoa Bui, Sagar S Damle, Stan Riney, Mark J Graham, Rosanne M Crooke, Stanley T Crooke
A variety of diseases are caused by deficiencies in amounts or activity of key proteins. An approach that increases the amount of a specific protein might be of therapeutic benefit. We reasoned that translation could be specifically enhanced using trans-acting agents that counter the function of negative regulatory elements present in the 5' UTRs of some mRNAs. We recently showed that translation can be enhanced by antisense oligonucleotides (ASOs) that target upstream open reading frames. Here we report the amount of a protein can also be selectively increased using ASOs designed to hybridize to other translation inhibitory elements in 5' UTRs...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28931862/long-non-coding-rna-hotair-promotes-cell-migration-by-upregulating-insulin-growth-factor-binding-protein-2-in-renal-cell-carcinoma
#4
Hiromichi Katayama, Keiichi Tamai, Rie Shibuya, Mao Nakamura, Mai Mochizuki, Kazunori Yamaguchi, Sadafumi Kawamura, Tatsuo Tochigi, Ikuro Sato, Takamasa Okanishi, Kunie Sakurai, Wataru Fujibuchi, Yoichi Arai, Kennichi Satoh
Renal cell carcinoma (RCC) is one of the most lethal urologic cancers. About one-third of RCC patients already have distal metastasis at the time of diagnosis. There is growing evidence that Hox antisense intergenic RNA (HOTAIR) plays essential roles in metastasis in several types of cancers. However, the precise mechanism by which HOTAIR enhances malignancy remains unclear, especially in RCC. Here, we demonstrated that HOTAIR enhances RCC-cell migration by regulating the insulin growth factor-binding protein 2 (IGFBP2) expression...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28928822/long-non-coding-rna-igf2as-controls-hepatocellular-carcinoma-progression-through-the-erk-mapk-signaling-pathway
#5
Han Bao, Chun-Guang Guo, Peng-Cheng Qiu, Xin-Lei Zhang, Qi Dong, Yu-Kun Wang
Long non-coding RNAs (lncRNAs) serve an important role in numerous human diseases, including cancer. Abnormal expression of lncRNAs has been associated with a number of tumor types; however, the underlying mechanisms through which lncRNA functions have yet to be elucidated. The present study primarily focuses on insulin-like growth factor 2 antisense 1 (Igf2as), a lncRNA reported to be differentially expressed in hepatocellular carcinoma (HCC). Reverse transcription-quantitative polymerase chain reaction analysis was used to determine the level of Igf2as in HCC cells and tissues...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28928151/comparative-analysis-reveals-genomic-features-of-stress-induced-transcriptional-readthrough
#6
Anna Vilborg, Niv Sabath, Yuval Wiesel, Jenny Nathans, Flonia Levy-Adam, Therese A Yario, Joan A Steitz, Reut Shalgi
Transcription is a highly regulated process, and stress-induced changes in gene transcription have been shown to play a major role in stress responses and adaptation. Genome-wide studies reveal prevalent transcription beyond known protein-coding gene loci, generating a variety of RNA classes, most of unknown function. One such class, termed downstream of gene-containing transcripts (DoGs), was reported to result from transcriptional readthrough upon osmotic stress in human cells. However, how widespread the readthrough phenomenon is, and what its causes and consequences are, remain elusive...
September 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28928022/the-role-of-jab1-a-putative-downstream-effector-of-the-neurotrophic-cytokine-macrophage-migration-inhibitory-factor-mif-in-zebrafish-inner-ear-hair-cell-development
#7
REVIEW
Loren J Weber, Hannah K Marcy, Yu-Chi Shen, Sarah E Tomkovich, Kristina M Brooks, Kelly E Hilk, Kate F Barald
Macrophage migration inhibitory factor (MIF) is a neurotrophic cytokine essential for inner ear hair cell (HC) development and statoacoustic ganglion (SAG) neurite outgrowth, and SAG survival in mouse, chick and zebrafish. Another neurotrophic cytokine, Monocyte chemoattractant protein 1 (MCP1) is known to synergize with MIF; but MCP1 alone is insufficient to support mouse/chick SAG neurite outgrowth or neuronal survival. Because of the relatively short time over which the zebrafish inner ear develops (~30h), the living zebrafish embryo is an ideal system to examine mif and mcp1 cytokine pathways and interactions...
September 16, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28926086/common-variants-in-dlg1-locus-are-associated-with-non-syndromic-cleft-lip-with-or-without-cleft-palate
#8
Adrianna Mostowska, Agnieszka Gaczkowska, Kacper Żukowski, Kerstin U Ludwig, Kamil K Hozyasz, Piotr Wójcicki, Elizabeth Mangold, Anne C Böhmer, Stefanie Heilmann-Heimbach, Michael Knapp, Małgorzata Zadurska, Barbara Biedziak, Margareta Budner, Agnieszka Lasota, Agata Daktera-Micker, Paweł P Jagodziński
Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a common craniofacial anomaly with a complex and heterogeneous etiology. Knowledge regarding specific genetic factors underlying this birth defect is still not well understood. Therefore, we conducted an independent replication analysis for the top-associated variants located within the DLG1 locus at chromosome 3q29, which was identified as a novel cleft-susceptibility locus in our genome-wide association study (GWAS). Mega-analysis of the pooled individual data from the GWAS and replication study confirmed that common DLG1 variants are associated with the risk of nsCL/P...
September 19, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28921648/rna-therapeutics-in-oncology-advances-challenges-and-future-directions
#9
A Robert MacLeod, Stanley T Crooke
RNA-based therapeutic technologies represent a rapidly expanding class of therapeutic opportunities with the power to modulate cellular biology in ways never before possible. With RNA-targeted therapeutics, inhibitors of previously undruggable proteins, gene expression modulators, and even therapeutic proteins can be rationally designed based on sequence information alone, something that is not possible with other therapeutic modalities. The most advanced RNA therapeutic modalities are antisense oligonucleotides (ASOs) and small interfering RNAs...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28920889/therapies-targeting-dna-and-rna-in-huntington-s-disease
#10
REVIEW
Edward J Wild, Sarah J Tabrizi
No disease-slowing treatment exists for Huntington's disease, but its monogenic inheritance makes it an appealing candidate for the development of therapies targeting processes close to its genetic cause. Huntington's disease is caused by CAG repeat expansions in the HTT gene, which encodes the huntingtin protein; development of therapies to target HTT transcription and the translation of its mRNA is therefore an area of intense investigation. Huntingtin-lowering strategies include antisense oligonucleotides and RNA interference targeting mRNA, and zinc finger transcriptional repressors and CRISPR-Cas9 methods aiming to reduce transcription by targeting DNA...
October 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28919479/fabp1-knockdown-in-human-enterocytes-impairs-proliferation-and-alters-lipid-metabolism
#11
Rodriguez Sawicki Luciana, Bottasso Arias Natalia María, Scaglia Natalia, Falomir Lockhart Lisandro Jorge, Franchini Gisela Raquel, Storch Judith, Córsico Betina
Fatty Acid-Binding Proteins (FABPs) are abundant intracellular proteins that bind long chain fatty acids (FA) and have been related with inmunometabolic diseases. Intestinal epithelial cells express two isoforms of FABPs: liver FABP (LFABP or FABP1) and intestinal FABP (IFABP or FABP2). They are thought to be associated with intracellular dietary lipid transport and trafficking towards diverse cell fates. But still their specific functions are not well understood. To study FABP1's functions, we generated an FABP1 knockdown model in Caco-2 cell line by stable antisense cDNA transfection (FABP1as)...
September 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28918051/lrrk2-antisense-oligonucleotides-ameliorate-%C3%AE-synuclein-inclusion-formation-in-a-parkinson-s-disease-mouse-model
#12
Hien Tran Zhao, Neena John, Vedad Delic, Karli Ikeda-Lee, Aneeza Kim, Andreas Weihofen, Eric E Swayze, Holly B Kordasiewicz, Andrew B West, Laura A Volpicelli-Daley
No treatments exist to slow or halt Parkinson's disease (PD) progression; however, inhibition of leucine-rich repeat kinase 2 (LRRK2) activity represents one of the most promising therapeutic strategies. Genetic ablation and pharmacological LRRK2 inhibition have demonstrated promise in blocking α-synuclein (α-syn) pathology. However, LRRK2 kinase inhibitors may reduce LRRK2 activity in several tissues and induce systemic phenotypes in the kidney and lung that are undesirable. Here, we test whether antisense oligonucleotides (ASOs) provide an alternative therapeutic strategy, as they can be restricted to the CNS and provide a stable, long-lasting reduction of protein throughout the brain...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918041/gapmer-antisense-oligonucleotides-suppress-the-mutant-allele-of-col6a3-and-restore-functional-protein-in-ullrich-muscular-dystrophy
#13
Elena Marrosu, Pierpaolo Ala, Francesco Muntoni, Haiyan Zhou
Dominant-negative mutations in the genes that encode the three major α chains of collagen type VI, COL6A1, COL6A2, and COL6A3, account for more than 50% of Ullrich congenital muscular dystrophy patients and nearly all Bethlem myopathy patients. Gapmer antisense oligonucleotides (AONs) are usually used for gene silencing by stimulating RNA cleavage through the recruitment of an endogenous endonuclease known as RNase H to cleave the RNA strand of a DNA-RNA duplex. In this study, we exploited the application of the allele-specific silencing approach by gapmer AON as a potential therapy for Collagen-VI-related congenital muscular dystrophy (COL6-CMD)...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918026/anti-fibrotic-effects-of-synthetic-oligodeoxynucleotide-for-tgf-%C3%AE-1-and-smad-in-an-animal-model-of-liver-cirrhosis
#14
Jung-Yeon Kim, Hyun-Jin An, Woon-Hae Kim, Mi-Gyeong Gwon, Hyemin Gu, Yoon-Yub Park, Kwan-Kyu Park
Liver fibrosis is characterized by changes in tissue architecture and extracellular matrix composition. Liver fibrosis affects not only hepatocytes but also the non-parenchymal cells such as hepatic stellate cells (HSCs), which are essential for maintaining an intact liver structure and function. Transforming growth factor β1 (TGF-β1) is a multifunctional cytokine that induces liver fibrosis through activation of Smad signaling pathways. To improve a new therapeutic approach, synthetic TGF-β1/Smad oligodeoxynucleotide (ODN) was used to suppress both TGF-β1 expression and Smad transcription factor using a combination of antisense ODN and decoy ODN...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918024/antisense-oligonucleotide-mediated-removal-of-the-polyglutamine-repeat-in-spinocerebellar-ataxia-type-3-mice
#15
Lodewijk J A Toonen, Frank Rigo, Haico van Attikum, Willeke M C van Roon-Mom
Spinocerebellar ataxia type 3 (SCA3) is a currently incurable neurodegenerative disorder caused by a CAG triplet expansion in exon 10 of the ATXN3 gene. The resultant expanded polyglutamine stretch in the mutant ataxin-3 protein causes a gain of toxic function, which eventually leads to neurodegeneration. One important function of ataxin-3 is its involvement in the proteasomal protein degradation pathway, and long-term downregulation of the protein may therefore not be desirable. In the current study, we made use of antisense oligonucleotides to mask predicted exonic splicing signals, resulting in exon 10 skipping from ATXN3 pre-mRNA...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917758/review-on-investigations-of-antisense-oligonucleotides-with-the-use-of-mass-spectrometry
#16
REVIEW
Sylwia Studzińska
Antisense oligonucleotides have been investigated as potential drugs for years. They inhibit target gene or protein expression. The present review summarizes their modifications, modes of action, and applications of liquid chromatography coupled with mass spectrometry for qualitative and quantitative analysis of these compounds. The most recent reports on a given topic were given prominence, while some early studies were reviewed in order to provide a theoretical background. The present review covers the issues of using ion-exchange chromatography, ion-pair reversed-phase high performance liquid chromatography and hydrophilic interaction chromatography for the separation of antisense oligonucleotides...
January 1, 2018: Talanta
https://www.readbyqxmd.com/read/28917589/a-novel-rgl2-dof6-complex-contributes-to-primary-seed-dormancy-in-arabidopsis-thaliana-by-regulating-a-gata-transcription-factor
#17
Pratibha Ravindran, Vivek Verma, Petra Stamm, Prakash P Kumar
The DELLA protein RGA-LIKE2 (RGL2) is a key transcriptional repressor of gibberellic acid (GA) signaling that regulates seed germination. We identified GATA12, a gene encoding a GATA-type zinc finger transcription factor, as one of the downstream targets of RGL2 in Arabidopsis thaliana. Our data show that freshly harvested (unstratified) seeds of GATA12 antisense suppression lines have reduced dormancy than the wild type, while ectopic expression lines show enhanced seed dormancy. We show that GATA12 transcription is negatively regulated by GA and its transcript levels decline dramatically under dormancy-breaking conditions such as dry storage and cold-stratification of seeds...
September 13, 2017: Molecular Plant
https://www.readbyqxmd.com/read/28912690/ring-finger-protein-38-is-a-neuronal-protein-in-the-brain-of-nile-tilapia-oreochromis-niloticus
#18
Kai Lin Cham, Tomoko Soga, Ishwar S Parhar
Really interesting new gene (RING) finger protein is a type of zinc-binding motif found in a large family of functionally distinct proteins. RING finger proteins are involved in diverse cellular processes including apoptosis, DNA repair, cell cycle, signal transduction, tumour suppressor, vesicular transport, and peroxisomal biogenesis. RING finger protein 38 (RNF38) is a member of the family whose functions remain unknown. To gain insight into the putative effects of RNF38 in the central nervous system, we localised its expression...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28912673/improving-the-delivery-of-sod1-antisense-oligonucleotides-to-motor-neurons-using-calcium-phosphate-lipid-nanoparticles
#19
Liyu Chen, Clare Watson, Marco Morsch, Nicholas J Cole, Roger S Chung, Darren N Saunders, Justin J Yerbury, Kara L Vine
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease affecting the upper and lower motor neurons in the motor cortex and spinal cord. Abnormal accumulation of mutant superoxide dismutase I (SOD1) in motor neurons is a pathological hallmark of some forms of the disease. We have shown that the orderly progression of the disease may be explained by misfolded SOD1 cell-to-cell propagation, which is reliant upon its active endogenous synthesis. Reducing the levels of SOD1 is therefore a promising therapeutic approach...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28911087/an-antisense-oligonucleotide-targeting-tgf-%C3%AE-2-inhibits-lung-metastasis-and-induces-cd86-expression-in-tumor-associated-macrophages
#20
I Huber-Ruano, C Raventós, I Cuartas, C Sánchez-Jaro, A Arias, J L Parra, K Wosikowski, M Janicot, J Seoane
Background: The transforming growth factor (TGF)-β pathway is a well-described inducer of immunosuppression and can act as an oncogenic factor in advanced tumors. Several preclinical and clinical studies show that the TGF-β pathway can be considered a promising molecular target for cancer therapy. The human genome has three TGF-β isoforms and not much is known about the oncogenic response to each of the isoforms. Here, we studied the antitumor response to ISTH0047, a recently developed locked nucleic acid-modified antisense oligonucleotide targeting TGF-β2...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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