Targeting of microRNAs for therapeutics

2008 ◽  
Vol 36 (6) ◽  
pp. 1197-1200 ◽  
Author(s):  
Jan Stenvang ◽  
Morten Lindow ◽  
Sakari Kauppinen
Keyword(s):  
Gene Expression ◽  
Cardiovascular Diseases ◽  
High Stability ◽  
Viral Infections ◽  
Modified Oligonucleotides ◽  
Rna Molecules ◽  
Locked Nucleic Acids ◽  
Non Coding Rnas ◽  
High Binding Affinity

miRNAs (microRNAs) comprise a class of small endogenous non-coding RNAs that post-transcriptionally repress gene expression by base-pairing with their target mRNAs. Recent evidence has shown that miRNAs play important roles in a wide variety of human diseases, such as viral infections, cancer and cardiovascular diseases, and thus miRNAs have rapidly emerged as potential targets for therapeutics. LNAs (locked nucleic acids) comprise a class of bicyclic conformational analogues of RNA, which exhibit high binding affinity to complementary RNA molecules and high stability in blood and tissues in vivo. Recent reports on LNA-mediated miRNA silencing in rodents and primates support the potential of LNA-modified oligonucleotides in studying miRNA functions in vivo and in the future development of miRNA-based therapeutics.

Abstract 286: Long Noncoding RNAs Are Differentially Expressed in Heart Failure

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Emma L Robinson ◽  
Syed Haider ◽  
Hillary Hei ◽  
Richard T Lee ◽  
Roger S Foo
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Significant Proportion ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Control Of Gene Expression ◽  
Failing Heart ◽  
Novel Transcripts ◽  
Non Coding Rnas

Heart failure comprises of clinically distinct inciting causes but a consistent pattern of change in myocardial gene expression supports the hypothesis that unifying biochemical mechanisms underlie disease progression. The recent RNA-seq revolution has enabled whole transcriptome profiling, using deep-sequencing technologies. Up to 70% of the genome is now known to be transcribed into RNA, a significant proportion of which is long non-coding RNAs (lncRNAs), defined as polyribonucleotides of ≥200 nucleotides. This project aims to discover whether the myocardium expression of lncRNAs changes in the failing heart. Paired end RNA-seq from a 300-400bp library of ‘stretched’ mouse myocyte total RNA was carried out to generate 76-mer sequence reads. Mechanically stretching myocytes with equibiaxial stretch apparatus mimics pathological hypertrophy in the heart. Transcripts were assembled and aligned to reference genome mm9 (UCSC), abundance determined and differential expression of novel transcripts and alternative splice variants were compared with that of control (non-stretched) mouse myocytes. Five novel transcripts have been identified in our RNA-seq that are differentially expressed in stretched myocytes compared with non-stretched. These are regions of the genome that are currently unannotated and potentially are transcribed into non-coding RNAs. Roles of known lncRNAs include control of gene expression, either by direct interaction with complementary regions of the genome or association with chromatin remodelling complexes which act on the epigenome.Changes in expression of genes which contribute to the deterioration of the failing heart could be due to the actions of these novel lncRNAs, immediately suggesting a target for new pharmaceuticals. Changes in the expression of these novel transcripts will be validated in a larger sample size of stretched myocytes vs non-stretched myocytes as well as in the hearts of transverse aortic constriction (TAC) mice vs Sham (surgical procedure without the aortic banding). In vivo investigations will then be carried out, using siLNA antisense technology to silence novel lncRNAs in mice.

scholarly journals Non-coding RNAs in cancers with chromosomal rearrangements: the signatures, causes, functions and implications

2019 ◽  
Vol 11 (10) ◽  
pp. 886-898 ◽  
Author(s):  
Cai Han ◽  
Lin-Yu Sun ◽  
Wen-Tao Wang ◽  
Yu-Meng Sun ◽  
Yue-Qin Chen
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Fusion Proteins ◽  
Gene Fusion ◽  
Chromosomal Rearrangements ◽  
Chromosomal Translocation ◽  
Chromosomal Translocations ◽  
Rna Molecules ◽  
Non Coding Rnas ◽  
The Relationship

Abstract Chromosomal translocation leads to the juxtaposition of two otherwise separate DNA loci, which could result in gene fusion. These rearrangements at the DNA level are catastrophic events and often have causal roles in tumorigenesis. The oncogenic DNA messages are transferred to RNA molecules, which are in most cases translated into cancerous fusion proteins. Gene expression programs and signaling pathways are altered in these cytogenetically abnormal contexts. Notably, non-coding RNAs have attracted increasing attention and are believed to be tightly associated with chromosome-rearranged cancers. These RNAs not only function as modulators in downstream pathways but also directly affect chromosomal translocation or the associated products. This review summarizes recent research advances on the relationship between non-coding RNAs and chromosomal translocations and on diverse functions of non-coding RNAs in cancers with chromosomal rearrangements.

scholarly journals Antiviral Activity of Resveratrol against Human and Animal Viruses

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Yusuf Abba ◽  
Hasliza Hassim ◽  
Hazilawati Hamzah ◽  
Mohamed Mustapha Noordin
Keyword(s):  
Gene Expression ◽  
Viral Infections ◽  
Antioxidant Properties ◽  
Acid Synthesis ◽  
Antioxidant Effect ◽  
Viral Diseases ◽  
Polyphenolic Compound ◽  
Antiviral Effects

Resveratrol is a potent polyphenolic compound that is being extensively studied in the amelioration of viral infections bothin vitroandin vivo. Its antioxidant effect is mainly elicited through inhibition of important gene pathways like the NF-κβpathway, while its antiviral effects are associated with inhibitions of viral replication, protein synthesis, gene expression, and nucleic acid synthesis. Although the beneficial roles of resveratrol in several viral diseases have been well documented, a few adverse effects have been reported as well. This review highlights the antiviral mechanisms of resveratrol in human and animal viral infections and how some of these effects are associated with the antioxidant properties of the compound.

scholarly journals Synthetic long non-coding RNAs [SINEUPs] rescue defective gene expression in vivo

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Alessia Indrieri ◽  
Claudia Grimaldi ◽  
Silvia Zucchelli ◽  
Roberta Tammaro ◽  
Stefano Gustincich ◽  
...  
Keyword(s):  
Gene Expression ◽  
Defective Gene ◽  
Non Coding Rnas

scholarly journals Enhancers predominantly regulate gene expression in vivo via transcription initiation

2019 ◽  
Author(s):  
Martin S. C. Larke ◽  
Takayuki Nojima ◽  
Jelena Telenius ◽  
Jacqueline A. Sharpe ◽  
Jacqueline A. Sloane-Stanley ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Transcription Initiation ◽  
Genetically Engineered ◽  
Control Gene ◽  
Transcriptional Initiation ◽  
Pol Ii ◽  
Rna Molecules ◽  
Control Gene Expression

ABSTRACTGene transcription occurs via a cycle of linked events including initiation, promoter proximal pausing and elongation of RNA polymerase II (Pol II). A key question is how do transcriptional enhancers influence these events to control gene expression? Here we have used a new approach to quantify transcriptional initiation and pausing in vivo, while simultaneously identifying transcription start sites (TSSs) and pause-sites (TPSs) from single RNA molecules. When analyzed in parallel with nascent RNA-seq, these data show that differential gene expression is achieved predominantly via changes in transcription initiation rather than Pol II pausing. Using genetically engineered mouse models deleted for specific enhancers we show that these elements control gene expression via Pol II recruitment and/or initiation rather than via promoter proximal pause release. Together, our data show that enhancers, in general, control gene expression predominantly by Pol II recruitment and initiation rather than via pausing.

scholarly journals Taenia solium microRNAs: Potential Biomarkers and Drug Targets in Neurocysticercosis

2021 ◽  
Author(s):  
Matías Gastón Pérez
Keyword(s):  
Gene Expression ◽  
Clinical Trials ◽  
Cell Growth ◽  
Drug Targets ◽  
Metabolic Diseases ◽  
Viral Infections ◽  
Taenia Solium ◽  
Non Coding Rnas ◽  
Host Parasite ◽  
Potential Biomarkers

MicroRNAs (miRNAs) found in animals, plants, and some viruses belongs to the heterogeneous class of non-coding RNAs (ncRNAs), which posttranscriptional regulates gene expression. They are linked to various cellular activities such as cell growth, differentiation, development and apoptosis. Also, they have been involved in cancer, metabolic diseases, viral infections and clinical trials targeting miRNAs has shown promising results. This chapter provides an overview on Taenia solium and Taenia crassiceps miRNAs, their possible biological functions, their role in host–parasite communication and their potential role as biomarkers and drug targets.

scholarly journals Research Progress on Plant Long Non-Coding RNA

Plants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 408
Author(s):  
Ling Wu ◽  
Sian Liu ◽  
Haoran Qi ◽  
Heng Cai ◽  
Meng Xu
Keyword(s):  
Growth And Development ◽  
Protein Modification ◽  
Plant Molecular Biology ◽  
Research Progress ◽  
Current Status ◽  
Sequence Length ◽  
Small Molecular Weight ◽  
Rna Molecules ◽  
Non Coding Rnas

Non-coding RNAs (ncRNAs) that were once considered “dark matter” or “transcriptional noise” in genomes are research hotspots in the field of epigenetics. The most well-known microRNAs (miRNAs) are a class of short non-coding, small molecular weight RNAs with lengths of 20–24 nucleotides that are highly conserved throughout evolution. Through complementary pairing with the bases of target sites, target gene transcripts are cleaved and degraded, or translation is inhibited, thus regulating the growth and development of organisms. Unlike miRNAs, which have been studied thoroughly, long non-coding RNAs (lncRNAs) are a group of poorly conserved RNA molecules with a sequence length of more than 200 nucleotides and no protein encoding capability; they interact with large molecules, such as DNA, RNA, and proteins, and regulate protein modification, chromatin remodeling, protein functional activity, and RNA metabolism in vivo through cis- or trans-activation at the transcriptional, post-transcriptional, and epigenetic levels. Research on plant lncRNAs is just beginning and has gradually emerged in the field of plant molecular biology. Currently, some studies have revealed that lncRNAs are extensively involved in plant growth and development and stress response processes by mediating the transmission and expression of genetic information. This paper systematically introduces lncRNA and its regulatory mechanisms, reviews the current status and progress of lncRNA research in plants, summarizes the main techniques and strategies of lncRNA research in recent years, and discusses existing problems and prospects, in order to provide ideas for further exploration and verification of the specific evolution of plant lncRNAs and their biological functions.

scholarly journals The Non-coding MicroRNA-223 is a Promising Biomarker of Chronic Kidney Disease

2021 ◽  
pp. 91-95
Author(s):  
Valerie Metzinger-Le Meuth ◽  
Laurent Metzinger
Keyword(s):  
Gene Expression ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Diseases ◽  
Mirna Regulation ◽  
Mrna Targets ◽  
Cardiovascular Damage ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation

Renal diseases are consecutive to a deregulation of gene expression regulated by non-coding RNAs. These non-coding RNAs were discovered at the turn of the 21st century when it was established that post-transcriptional regulation was performed through small non-coding RNAs, known as microRNAs (miRNAs). Up to 3,000 miRNAs are expressed by human cells. They are small, single-stranded nucleic acids, which trigger translational repression of mRNA by base-pairing with the 3′ untranslated region of their mRNA targets. In addition to miRNA regulation, it was also demonstrated that 60,000 long non-coding RNAs are expressed in the human cell and that they are able to regulate gene expression at all levels. The roles of these various RNA families are just beginning to be understood in the field of nephrology. In the past decade, the authors and various others have published that several miRNAs are deregulated during the onset of chronic kidney disease (CKD) and are associated with cardiovascular damage. This review focuses on miRNA-223 (miR-223) as its expression is increased in vivo in the large vessels of a mouse model of CKD, whereas it is diminished in the serum of both mice and human patients with CKD. In patients, miR-223 expression was correlated with all-cause mortality, as well as cardiovascular and renal events. Molecular clues were given by a multi-omics approach, indicating that miR-223 modulates gene regulation at all levels including mRNA expression, protein amounts, and metabolic molecule accumulation. miR-223 is thus a potential target to prevent or treat complications of CKD pathogenesis.

scholarly journals SARS-CoV-2, Cardiovascular Diseases and Noncoding RNAs: A Connected Triad

2021 ◽  
Vol 22 (22) ◽  
pp. 12243
Author(s):  
Lucia Natarelli ◽  
Fabio Virgili ◽  
Christian Weber
Keyword(s):  
Gene Expression ◽  
Cardiovascular Diseases ◽  
Regulation Of Gene Expression ◽  
Noncoding Rnas ◽  
Adverse Outcomes ◽  
Rna Molecules ◽  
Clinical Level ◽  
Important Target ◽  
Stable Conditions

Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is characterized by important respiratory impairments frequently associated with severe cardiovascular damages. Moreover, patients with pre-existing comorbidity for cardiovascular diseases (CVD) often present a dramatic increase in inflammatory cytokines release, which increases the severity and adverse outcomes of the infection and, finally, mortality risk. Despite this evident association at the clinical level, the mechanisms linking CVD and COVID-19 are still blurry and unresolved. Noncoding RNAs (ncRNAs) are functional RNA molecules transcribed from DNA but usually not translated into proteins. They play an important role in the regulation of gene expression, either in relatively stable conditions or as a response to different stimuli, including viral infection, and are therefore considered a possible important target in the design of specific drugs. In this review, we introduce known associations and interactions between COVID-19 and CVD, discussing the role of ncRNAs within SARS-CoV-2 infection from the perspective of the development of efficient pharmacological tools to treat COVID-19 patients and taking into account the equally dramatic associated consequences, such as those affecting the cardiovascular system.

scholarly journals MicroRNA regulation of vascular function

2019 ◽  
Vol 1 (1) ◽  
pp. H41-H46
Author(s):  
David Mellis ◽  
Andrea Caporali
Keyword(s):  
Gene Expression ◽  
Therapeutic Intervention ◽  
Vascular Function ◽  
State Of The Art ◽  
Genetic Networks ◽  
Mirna Biogenesis ◽  
Technical Feasibility ◽  
Microrna Regulation ◽  
Non Coding Rnas

MicroRNAs (miRNAs) are small non-coding RNAs that orchestrate genetic networks by modulating gene expression. Given their importance in vascular development, homeostasis and diseases, along with the technical feasibility in deploying their function in vivo, the so-called ‘vascular miRNAs’ have become key targets for therapeutic intervention. Herein, we have summarised the state-of-the-art on vascular miRNAs and we have discussed the role miRNA biogenesis and the extracellular vesicles (EVs) miRNA transport in vascular biology.

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