scholarly journals Adding a “Notch” to Cardiovascular Disease Therapeutics: A MicroRNA-Based Approach

2021 ◽  
Vol 9 ◽  
Author(s):  
Luisa Marracino ◽  
Francesca Fortini ◽  
Esmaa Bouhamida ◽  
Francesca Camponogara ◽  
Paolo Severi ◽  
...  
Keyword(s):  
Cardiovascular System ◽  
Molecular Mechanisms ◽  
Notch Pathway ◽  
Biological Processes ◽  
Rna Sequences ◽  
Regulate Gene Expression ◽  
Cellular Processes ◽  
Non Coding Rna ◽  
Mirnas Expression

Dysregulation of the Notch pathway is implicated in the pathophysiology of cardiovascular diseases (CVDs), but, as of today, therapies based on the re-establishing the physiological levels of Notch in the heart and vessels are not available. A possible reason is the context-dependent role of Notch in the cardiovascular system, which would require a finely tuned, cell-specific approach. MicroRNAs (miRNAs) are short functional endogenous, non-coding RNA sequences able to regulate gene expression at post-transcriptional levels influencing most, if not all, biological processes. Dysregulation of miRNAs expression is implicated in the molecular mechanisms underlying many CVDs. Notch is regulated and regulates a large number of miRNAs expressed in the cardiovascular system and, thus, targeting these miRNAs could represent an avenue to be explored to target Notch for CVDs. In this Review, we provide an overview of both established and potential, based on evidence in other pathologies, crosstalks between miRNAs and Notch in cellular processes underlying atherosclerosis, myocardial ischemia, heart failure, calcification of aortic valve, and arrhythmias. We also discuss the potential advantages, as well as the challenges, of using miRNAs for a Notch-based approach for the diagnosis and treatment of the most common CVDs.

scholarly journals Role of Long Non-Coding RNA Polymorphisms in Cancer Chemotherapeutic Response

2021 ◽  
Vol 11 (6) ◽  
pp. 513
Author(s):  
Zheng Zhang ◽  
Meng Gu ◽  
Zhongze Gu ◽  
Yan-Ru Lou
Keyword(s):  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Cellular Processes ◽  
Dna And Rna ◽  
Chemotherapeutic Response ◽  
Non Coding Rna ◽  
Response To Chemotherapy ◽  
Personalized Oncology ◽  
Long Non Coding Rna

Genetic polymorphisms are defined as the presence of two or more different alleles in the same locus, with a frequency higher than 1% in the population. Since the discovery of long non-coding RNAs (lncRNAs), which refer to a non-coding RNA with a length of more than 200 nucleotides, their biological roles have been increasingly revealed in recent years. They regulate many cellular processes, from pluripotency to cancer. Interestingly, abnormal expression or dysfunction of lncRNAs is closely related to the occurrence of human diseases, including cancer and degenerative neurological diseases. Particularly, their polymorphisms have been found to be associated with altered drug response and/or drug toxicity in cancer treatment. However, molecular mechanisms are not yet fully elucidated, which are expected to be discovered by detailed studies of RNA–protein, RNA–DNA, and RNA–lipid interactions. In conclusion, lncRNAs polymorphisms may become biomarkers for predicting the response to chemotherapy in cancer patients. Here we review and discuss how gene polymorphisms of lncRNAs affect cancer chemotherapeutic response. This knowledge may pave the way to personalized oncology treatments.

scholarly journals MiR-155: An Important Regulator of Neuroinflammation

2021 ◽  
Vol 23 (1) ◽  
pp. 90
Author(s):  
Valeria Domenica Zingale ◽  
Agnese Gugliandolo ◽  
Emanuela Mazzon
Keyword(s):  
Neurological Diseases ◽  
Transcriptional Level ◽  
Regulate Gene Expression ◽  
Rna Molecules ◽  
Cellular Processes ◽  
Non Coding Rna ◽  
Important Regulator ◽  
The Central Nervous System ◽  
High Concentrations ◽  
Mirnas Expression

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level and that play an important role in many cellular processes, including modulation of inflammation. MiRNAs are present in high concentrations in the central nervous system (CNS) and are spatially and temporally expressed in a specific way. Therefore, an imbalance in the expression pattern of these small molecules can be involved in the development of neurological diseases. Generally, CNS responds to damage or disease through the activation of an inflammatory response, but many neurological disorders are characterized by uncontrolled neuroinflammation. Many studies support the involvement of miRNAs in the activation or inhibition of inflammatory signaling and in the promotion of uncontrolled neuroinflammation with pathological consequences. MiR-155 is a pro-inflammatory mediator of the CNS and plays an important regulatory role. The purpose of this review is to summarize how miR-155 is regulated and the pathological consequences of its deregulation during neuroinflammatory disorders, including multiple sclerosis, Alzheimer’s disease and other neuroinflammatory disorders. Modulation of miRNAs’ expression could be used as a therapeutic strategy in the treatment of pathological neuroinflammation.

scholarly journals Identification and Functional Prediction of Drought-Responsive Long Non-Coding RNA in Tomato

Agronomy ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 629 ◽  
Author(s):  
Seung Hee Eom ◽  
Hee Ju Lee ◽  
Jin Hyoung Lee ◽  
Seung Hwan Wi ◽  
Sung Kyeom Kim ◽  
...  
Keyword(s):  
Higher Plants ◽  
Biological Processes ◽  
Mrna Targets ◽  
Non Coding Rna ◽  
Starting Point ◽  
Antisense Lncrnas ◽  
Non Coding Rnas ◽  
Mirnas Expression ◽  
Long Non Coding Rna

In higher plants, several lines of evidence suggest that long non-coding RNAs (lncRNAs) may play important roles in the regulation of various biological processes by regulating gene expression. In this study, we identified a total of 521 lncRNAs, classified as intergenic, intronic, sense, and natural antisense lncRNAs, from RNA-seq data of drought-exposed tomato leaves. A further 244 drought-responsive tomato lncRNAs were predicted to be putative targets of 92 tomato miRNAs. Expression pattern and preliminary functional analysis of potential mRNA targets suggested that drought-responsive tomato lncRNAs play important roles in a variety of biological processes via lncRNA–mRNA co-expression. Taken together, these data present a comprehensive view of drought-responsive tomato lncRNAs that serve as a starting point for understanding the role of long intergenic non-coding RNAs in the regulatory mechanisms underlying drought responses in crops.

scholarly journals Notch Signaling Regulation in Autoinflammatory Diseases

2020 ◽  
Vol 21 (22) ◽  
pp. 8847
Author(s):  
Rossella Gratton ◽  
Paola Maura Tricarico ◽  
Adamo Pio d'Adamo ◽  
Anna Monica Bianco ◽  
Ronald Moura ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Notch Pathway ◽  
Autoinflammatory Diseases ◽  
Cellular Processes ◽  
Core Components

Notch pathway is a highly conserved intracellular signaling route that modulates a vast variety of cellular processes including proliferation, differentiation, migration, cell fate and death. Recently, the presence of a strict crosstalk between Notch signaling and inflammation has been described, although the precise molecular mechanisms underlying this interplay have not yet been fully unravelled. Disruptions in Notch cascade, due both to direct mutations and/or to an altered regulation in the core components of Notch signaling, might lead to hypo- or hyperactivation of Notch target genes and signaling molecules, ultimately contributing to the onset of autoinflammatory diseases. To date, alterations in Notch signaling have been reported as associated with three autoinflammatory disorders, therefore, suggesting a possible role of Notch in the pathogenesis of the following diseases: hidradenitis suppurativa (HS), Behçet disease (BD), and giant cell arteritis (GCA). In this review, we aim at better characterizing the interplay between Notch and autoinflammatory diseases, trying to identify the role of this signaling route in the context of these disorders.

scholarly journals Long Non-Coding RNA MEG3 in Cellular Stemness

2021 ◽  
Vol 22 (10) ◽  
pp. 5348
Author(s):  
Pei-Fang Hsieh ◽  
Cheng-Chia Yu ◽  
Pei-Ming Chu ◽  
Pei-Ling Hsieh
Keyword(s):  
Stem Cells ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cellular Processes ◽  
Lineage Differentiation ◽  
Non Coding Rna ◽  
Regulatory Functions ◽  
Long Non Coding Rna ◽  
Large Repertoire

Long non-coding RNAs (lncRNAs) regulate a diverse array of cellular processes at the transcriptional, post-transcriptional, translational, and post-translational levels. Accumulating evidence suggests that lncRNA MEG3 exerts a large repertoire of regulatory functions in cellular stemness. This review focuses on the molecular mechanisms by which lncRNA MEG3 functions as a signal, scaffold, guide, and decoy for multi-lineage differentiation and even cancer progression. The role of MEG3 in various types of stem cells and cancer stem cells is discussed. Here, we provide an overview of the functional versatility of lncRNA MEG3 in modulating pluripotency, differentiation, and cancer stemness.

scholarly journals The Role of MicroRNAs in Antiarrhythmic Therapy for Atrial Fibrillation

2015 ◽  
Vol 4 (3) ◽  
pp. 146 ◽  
Author(s):  
Sebastian Clauss ◽  
Moritz F Sinner ◽  
Stefan Kääb ◽  
Reza Wakili ◽  
◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Molecular Mechanisms ◽  
Calcium Handling ◽  
Ectopic Activity ◽  
Atrial Fibrosis ◽  
Key Factors ◽  
Regulate Gene Expression ◽  
Non Coding Rna ◽  
Rna Fragments

Atrial fibrillation (AF) is the most common arrhythmia worldwide and has an enormous impact on our healthcare system as it is a major contributor of morbidity and mortality. Although there are several therapeutic options available, treatment of AF still remains challenging. AF pathophysiology is complex and still incompletely understood. In general, our understanding of AF is based on two mechanistic paradigms as functional hallmarks of AF: ectopic activity and reentry. Both ectopic activity and reentry are the result of remodelling processes. Functional and/or expressional changes in ion channels, connexins or calcium-handling proteins are important factors in electrical remodelling, whereas signalling processes leading to atrial dilatation and atrial fibrosis are key factors of structural remodelling. In recent years, new intriguing key players in AF pathophysiology have been identified: microRNAs (miRNAs). MiRNAs are short, non-coding RNA fragments that can regulate gene expression and have been demonstrated as important modifiers in signalling cascades leading to electrical and structural remodelling. In this article we review the miRNA-mediated molecular mechanisms underlying AF with special emphasis on the perspective of miRNAs as potential therapeutic targets for AF treatment.

scholarly journals The Role of Epac in Cancer Progression

2020 ◽  
Vol 21 (18) ◽  
pp. 6489 ◽  
Author(s):  
Nadine Wehbe ◽  
Hasan Slika ◽  
Joelle Mesmar ◽  
Suzanne A. Nasser ◽  
Gianfranco Pintus ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Effector Protein ◽  
Cancer Cell Proliferation ◽  
Biological Processes ◽  
Oxygen Species ◽  
Malignant Phenotype ◽  
Cellular Processes ◽  
Underlying Mechanisms

Cancer continues to be a prime contributor to global mortality. Despite tremendous research efforts and major advances in cancer therapy, much remains to be learned about the underlying molecular mechanisms of this debilitating disease. A better understanding of the key signaling events driving the malignant phenotype of cancer cells may help identify new pharmaco-targets. Cyclic adenosine 3′,5′-monophosphate (cAMP) modulates a plethora of biological processes, including those that are characteristic of malignant cells. Over the years, most cAMP-mediated actions were attributed to the activity of its effector protein kinase A (PKA). However, studies have revealed an important role for the exchange protein activated by cAMP (Epac) as another effector mediating the actions of cAMP. In cancer, Epac appears to have a dual role in regulating cellular processes that are essential for carcinogenesis. In addition, the development of Epac modulators offered new routes to further explore the role of this cAMP effector and its downstream pathways in cancer. In this review, the potentials of Epac as an attractive target in the fight against cancer are depicted. Additionally, the role of Epac in cancer progression, namely its effect on cancer cell proliferation, migration/metastasis, and apoptosis, with the possible interaction of reactive oxygen species (ROS) in these phenomena, is discussed with emphasis on the underlying mechanisms and pathways.

scholarly journals LONG NON-CODING RNAS AS REGULATORS OF PHYSIOLOGICAL AND PATHOLOGICAL PROCESSES OF THE CARDIOVASCULAR SYSTEM

2020 ◽  
Vol 66 (4) ◽  
pp. 72-84
Author(s):  
M. Khetsuriani ◽  
◽  
V. Dosenko ◽  
Keyword(s):  
Cardiovascular System ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Myocardial Damage ◽  
Muscle Dysfunction ◽  
Cardiac Cell ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Smooth Muscle Dysfunction

A large part of the human genome is transcribed into non-coding RNA. This review focuses on long noncoding RNAs (lncRNAs) involved in the regulation of gene expression. We considered information about the molecular mechanisms of of lncRNAs functioning, features of their interaction with miRNAs, mRNAs, DNA and the participation of lncRNAs in physiological and pathological processes of the cardiovascular system. In particular, the review shows the role of lncRNAs in cardiac cell differentiation, ischemic myocardial damage, cardiac hypertrophy, endothelial and smooth muscle dysfunction. Significant changes in the expression of individual lncRNAs in cardiac pathologies allow the use of these molecules for diagnostic purposes and as possible therapeutic targets.

scholarly journals The Role of Extracellular Vesicles as Shuttles of RNA and Their Clinical Significance as Biomarkers in Hepatocellular Carcinoma

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 902
Author(s):  
Eva Costanzi ◽  
Carolina Simioni ◽  
Gabriele Varano ◽  
Cinzia Brenna ◽  
Ilaria Conti ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Extracellular Vesicles ◽  
Tumor Metastasis ◽  
Biological Processes ◽  
Rna Molecules ◽  
Expression Of Genes ◽  
Non Coding Rna ◽  
Donor Cells ◽  
Relevant Role

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA). Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In liver, EVs play a crucial role in regulating cell–cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo. This review aims to discuss the rising role of EVs and their ncRNAs content in regulating specific aspects of hepatocellular carcinoma development, including tumorigenesis, angiogenesis, and tumor metastasis. We analyze the progress in EV-ncRNAs’ potential clinical applications as important diagnostic and prognostic biomarkers for liver conditions.

Structure, Function, Involvement in Diseases and Targeting of 14-3-3 Proteins: An Update

2018 ◽  
Vol 25 (1) ◽  
pp. 5-21 ◽  
Author(s):  
Ylenia Cau ◽  
Daniela Valensin ◽  
Mattia Mori ◽  
Sara Draghi ◽  
Maurizio Botta
Keyword(s):  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Physiological Role ◽  
Specific Protein ◽  
Protein Protein Interactions ◽  
Cellular Processes ◽  
Protein Partners ◽  
High Sequence Homology ◽  
Small Molecule Modulators

14-3-3 is a class of proteins able to interact with a multitude of targets by establishing protein-protein interactions (PPIs). They are usually found in all eukaryotes with a conserved secondary structure and high sequence homology among species. 14-3-3 proteins are involved in many physiological and pathological cellular processes either by triggering or interfering with the activity of specific protein partners. In the last years, the scientific community has collected many evidences on the role played by seven human 14-3-3 isoforms in cancer or neurodegenerative diseases. Indeed, these proteins regulate the molecular mechanisms associated to these diseases by interacting with (i) oncogenic and (ii) pro-apoptotic proteins and (iii) with proteins involved in Parkinson and Alzheimer diseases. The discovery of small molecule modulators of 14-3-3 PPIs could facilitate complete understanding of the physiological role of these proteins, and might offer valuable therapeutic approaches for these critical pathological states.

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