scholarly journals MicroRNA-based therapeutics in cardiovascular disease: screening and delivery to the target

2017 ◽  
Vol 46 (1) ◽  
pp. 11-21 ◽  
Author(s):  
David Mellis ◽  
Andrea Caporali

MicroRNAs (miRNAs) are small non-coding RNAs of ∼22 nucleotides, which have increasingly been recognized as potent post-transcriptional regulators of gene expression. MiRNA targeting is defined by the complementarities between positions 2–8 of miRNA 5′-end with generally the 3′-untranslated region of target mRNAs (messenger RNAs). The capacity of miRNAs to simultaneously inhibit many different mRNAs allows for an amplification of biological responses. Hence, miRNAs are extremely attractive targets for therapeutic regulation in several diseases, including cardiovascular. Novel approaches are emerging to identify the miRNA functions in cardiovascular biology processes and to improve miRNA delivery in the heart and vasculature. In the present study, we provide an overview of current studies of miRNA functions in cardiovascular cells by the use of high-content screening. We also discuss the challenge to achieve a safe and targeted delivery of miRNA therapeutics in cardiovascular cells.

2016 ◽  
Vol 38 (2) ◽  
pp. 427-448 ◽  
Author(s):  
Yanping Gao ◽  
Bing Feng ◽  
Siqi Han ◽  
Kai Zhang ◽  
Jing Chen ◽  
...  

Cancer remains one of the most threatening causes of human health impairment, and the mechanisms underlying tumorigenesis have not been completely characterized. MicroRNAs (miRNAs) are a group of endogenous, small (18∼25 nucleotides) non-coding RNAs which negatively regulate gene expressions by directly binding to the 3'-untranslated regions (3'-UTRs) of the target messenger RNAs (mRNAs). Increasing evidence has demonstrated abnormal miRNA profiles and confirmed their involvement in tumor initiation and progression. As one important member of the miR-200 family, microRNA (miR)-141 is aberrantly expressed in many human malignant tumors, participating in various cellular processes including epithelial-mesenchymal transition (EMT), proliferation, migration, invasion, and drug resistance. In the present review, we briefly describe the mechanisms underlying miR-141-mediated tumorigenesis and the possible future of miR-141 as a potential diagnostic and prognostic parameter as well as therapeutic target in clinical applications.


2008 ◽  
Vol 114 (12) ◽  
pp. 699-706 ◽  
Author(s):  
Chunxiang Zhang

miRNAs (microRNAs) comprise a novel class of endogenous, small, non-coding RNAs that negatively regulate gene expression via degradation or translational inhibition of their target mRNAs. Recent studies have demonstrated that miRNAs are highly expressed in the cardiovascular system. Although we are currently in the initial stages of understanding how this novel class of gene regulators is involved in cardiovascular biological functions, a growing body of exciting evidence suggests that miRNAs are important regulators of cardiovascular cell differentiation, growth, proliferation and apoptosis. Moreover, miRNAs are key modulators of both cardiovascular development and angiogenesis. Consequently, dysregulation of miRNA function may lead to cardiovascular diseases. Indeed, several recent reports have demonstrated that miRNAs are aberrantly expressed in diseased hearts and vessels. Modulating these aberrantly expressed miRNAs has significant effects on cardiac hypertrophy, vascular neointimal lesion formation and cardiac arrhythmias. Identifying the roles of miRNAs and their target genes and signalling pathways in cardiovascular disease will be critical for future research. miRNAs may represent a new layer of regulators for cardiovascular biology and a novel class of therapeutic targets for cardiovascular diseases.


2021 ◽  
Vol 16 ◽  
Author(s):  
Manu Madhavan ◽  
Gopakumar G

Background: Heart failure (HF) is a leading cause of mortality rate worldwide, but studied less for its underlying biomolecular mechanisms. With the advances in gene sequence analysis, many non-coding RNAs, especially from long non-coding RNA (lncRNA) genre are found to be involved in regulating HF conditions. Recent studies are based on competing endogenous RNA (ceRNA) theory in which lncRNA-miRNA-mRNA compounds control many disease conditions. Method: In this paper, we present a topic model based network cluster analysis to identify the role of lncRNAs in HF. The network is constructed based on the differentially expressed long non-coding RNAs (lncRNAs), micro RNAs (miRNAs), and messenger RNAs (mRNAs) of heart failure patients and control samples from the gene expression omnibus (GEO) database. Further, we extend the primary ceRNA network by adding pathways as additional nodes. Deep belief network based feature learning is used to extract the features from the network automatically. Results: We obtained two clusters where each cluster was a mixture of lncRNAs, mRNAs, miRNAs and pathways. The analysis included the identification of key lncRNAs, enriched pathways, and gene ontology terms from each cluster. Based on the shreds of evidence from literature, one of the clusters obtained was identified to be an essential functional module in HF mechanism. The potential of lncRNA as a diagnostic biomarker in HF was also analysed.


2020 ◽  
Vol 11 (11) ◽  
pp. 713-732
Author(s):  
Abhishek Kanugo ◽  
Ambikanandan Misra

The advancement of the oral route for macromolecules has gained a lot of attention due to its noninvasive nature, safe and challenging in active research but with limited success. Oral administration poses challenges due to poor solubility, short half-life, quick elimination and the physical, chemical and biological barriers of the gastrointestinal tract. Approaches of past for improving oral absorption, such as enhancers, mucoadhesive delivery and enzyme inhibitors have been taken over by novel approaches like advanced liposomes, self-nanoemulsifying drug delivery system, nanoparticles and targeted delivery. Eudratech™ Pep, Peptelligence, Rani Pill and Pharm Film are the emerging technologies for delivering oral proteins and peptide. Calcitonin, semaglutide and octreotide are the peptides available in the market for oral delivery as outcomes of these technologies.


Gene ◽  
2019 ◽  
Vol 697 ◽  
pp. 184-193 ◽  
Author(s):  
Yan-Hui Shi ◽  
Xin-Wei He ◽  
Feng-Di Liu ◽  
Yi-Sheng Liu ◽  
Yue Hu ◽  
...  

2018 ◽  
Vol 16 (02) ◽  
pp. 1840013 ◽  
Author(s):  
Oxana A. Volkova ◽  
Yury V. Kondrakhin ◽  
Timur A. Kashapov ◽  
Ruslan N. Sharipov

RNA plays an important role in the intracellular cell life and in the organism in general. Besides the well-established protein coding RNAs (messenger RNAs, mRNAs), long non-coding RNAs (lncRNAs) have gained the attention of recent researchers. Although lncRNAs have been classified as non-coding, some authors reported the presence of corresponding sequences in ribosome profiling data (Ribo-seq). Ribo-seq technology is a powerful experimental tool utilized to characterize RNA translation in cell with focus on initiation (harringtonine, lactimidomycin) and elongation (cycloheximide). By exploiting translation starts obtained from the Ribo-seq experiment, we developed a novel position weight matrix model for the prediction of translation starts. This model allowed us to achieve 96% accuracy of discrimination between human mRNAs and lncRNAs. When the same model was used for the prediction of putative ORFs in RNAs, we discovered that the majority of lncRNAs contained only small ORFs ([Formula: see text][Formula: see text]nt) in contrast to mRNAs.


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