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Noncoding RNAs in Regulatory Circuitries Underlying Neuronal Differentiation, Function and Disease

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 10902

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Prof. Dr. Dagmara Mirowska-Guzel

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Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CePT, Banacha 1B, 02-097 Warsaw, Poland
Interests: neurology; clinical pharmacology with special emphasis on drug safety, immunology and treatment of multiple sclerosis, neurotrophic factors in pathogenesis and course of neurological and cardiovascular diseases

Prof. Dr. Marek Postuła

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Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, Warsaw, Poland
Interests: pharmacogenomics; miRNA; diabetes; stroke; cardiovascular diseases; acute coronary syndrome; heart failure
Special Issues, Collections and Topics in MDPI journals

Dr. Ceren Eyileten

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Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology, Medical University of Warsaw, Warsaw, Poland
Interests: genomics; pharmacology

Special Issue Information

Dear Colleagues,

Non-coding RNAs (ncRNAs) play a role in numerous biological processes like cell proliferation, differentiation, apoptosis, and metabolism as well as stem cell self-renewal, survival and maintenance of cell integrity, formation of synapses, and DNA damage responses, through the suppression or activation of gene expression. Interestingly, ncRNAs are particularly abundant in the central nervous system and alterations in their expression pattern have been linked to neuronal differentiation, function and may lead to brain aging and neurodegenerative diseases. NcRNAs can modulate signaling pathways known to play a role in the pathophysiology of progressive neuronal dysfunction including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, and ischemic stroke Therefore, they pose as promising biomarkers and treatment for the vast majority of neurodegenerative disorders. However, there is limited knowledge of ncRNAs, and their impact on pathogenesis of neuronal degeneration. All research related to the described area, including systematic reviews, original research, review articles as well as comprehensive case reports are highly welcomed for submission.

Prof. Dr. Dagmara Mirowska-Guzel
Prof. Dr. Marek Postula
Dr. Ceren Eyileten
Guest Editors

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Keywords

ncRNA
miRNA
lncRNA
circRNA
piRNAs
siRNA
neuronal dysfunction
neuronal degeneration
neurodegenerative disorders
novel biomarker
novel therapeutics

Published Papers (4 papers)

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Research

Jump to: Review

15 pages, 4447 KiB

Open AccessArticle

Profile of TREM2-Derived circRNA and mRNA Variants in the Entorhinal Cortex of Alzheimer’s Disease Patients

by Amaya Urdánoz-Casado, Javier Sánchez-Ruiz de Gordoa, Maitane Robles, Miren Roldan, María Victoria Zelaya, Idoia Blanco-Luquin and Maite Mendioroz

Int. J. Mol. Sci. 2022, 23(14), 7682; https://doi.org/10.3390/ijms23147682 - 12 Jul 2022

Cited by 6 | Viewed by 2160

Abstract

Genetic variants in TREM2, a microglia-related gene, are well-known risk factors for Alzheimer’s disease (AD). Here, we report that TREM2 originates from circular RNAs (circRNAs), a novel class of non-coding RNAs characterized by a covalent and stable closed-loop structure. First, divergent primers were designed to amplify circRNAs by RT-PCR, which were further assessed by Sanger sequencing. Then, additional primer sets were used to confirm back-splicing junctions. In addition, HMC3 cells were used to assess the microglial expression of circTREM2s. Three candidate circTREM2s were identified in control and AD human entorhinal samples. One of the circRNAs, circTREM2_1, was consistently amplified by all divergent primer sets in control and AD entorhinal cortex samples as well as in HMC3 cells. In AD cases, a moderate negative correlation (r = −0.434) was found between the global average area of Aβ deposits in the entorhinal cortex and circTREM2_1 expression level. In addition, by bioinformatics tools, a total of 16 miRNAs were predicted to join with circTREM2s. Finally, TREM2 mRNA corresponding to four isoforms was profiled by RT-qPCR. TREM2 mRNA levels were found elevated in entorhinal samples of AD patients with low or intermediate ABC scores compared to controls. To sum up, a novel circRNA derived from the TREM2 gene, circTREM2_1, has been identified in the human entorhinal cortex and TREM2 mRNA expression has been detected to increase in AD compared to controls. Unraveling the molecular genetics of the TREM2 gene may help to better know the innate immune response in AD. Full article

(This article belongs to the Special Issue Noncoding RNAs in Regulatory Circuitries Underlying Neuronal Differentiation, Function and Disease)

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17 pages, 2288 KiB

Open AccessArticle

Diagnostic Performance of Circulating miRNAs and Extracellular Vesicles in Acute Ischemic Stroke

by Ceren Eyileten, Daniel Jakubik, Andleeb Shahzadi, Aleksandra Gasecka, Edwin van der Pol, Salvatore De Rosa, Dominika Siwik, Magdalena Gajewska, Dagmara Mirowska-Guzel, Iwona Kurkowska-Jastrzebska, Anna Czlonkowska and Marek Postula

Int. J. Mol. Sci. 2022, 23(9), 4530; https://doi.org/10.3390/ijms23094530 - 20 Apr 2022

Cited by 7 | Viewed by 2559

Abstract

Background: Increased inflammation activates blood coagulation system, higher platelet activation plays a key role in the pathophysiology of ischemic stroke (IS). During platelet activation and aggregation process, platelets may cause increased release of several proinflammatory, and prothrombotic mediators, including microRNAs (miRNAs) and extracellular vesicles (EVs). In the current study we aimed to assess circulating miRNAs profile related to platelet function and inflammation and circulating EVs from platelets, leukocytes, and endothelial cells to analyse their diagnostic and predictive utility in patients with acute IS. Methods: The study population consisted of 28 patients with the diagnosis of the acute IS. The control group consisted of 35 age- and gender-matched patients on acetylsalicylic acid (ASA) therapy without history of stroke and/or TIA with established stable coronary artery disease (CAD) and concomitant cardiovascular risk factors. Venous blood samples were collected from the control group and patients with IS on ASA therapy (a) 24 h after onset of acute IS, (b) 7-days following index hospitalization. Flow cytometry was used to determine the concentration of circulating EVs subtypes (from platelets, leukocytes, and endothelial cells) in platelet-depleted plasma and qRT-PCR was used to determine several circulating plasma miRNAs (miR-19a-3p, miR-186-5p and let-7f). Results: Patients with high platelet reactivity (HPR, based on arachidonic acid-induced platelet aggregometry) had significantly elevated platelet-EVs (CD62+) and leukocyte-EVs (CD45+) concentration compared to patients with normal platelet reactivity at the day of 1 acute-stroke (p = 0.012, p = 0.002, respectively). Diagnostic values of baseline miRNAs and EVs were evaluated with receiver operating characteristic (ROC) curve analysis. The area under the ROC curve for miR-19a-3p was 0.755 (95% CI, 0.63–0.88) p = 0.004, for let-7f, it was 0.874 (95% CI, 0.76–0.99) p = 0.0001; platelet-EVs was 0.776 (95% CI, 0.65–0.90) p = 0.001, whereas for leukocyte-EVs, it was 0.715 (95% CI, 0.57–0.87) p = 0.008. ROC curve showed that pooling the miR-19a-3p expressions, platelet-EVs, and leukocyte-EVs concentration yielded a higher AUC than the value of each individual biomarker as AUC was 0.893 (95% CI, 0.79–0.99). Patients with moderate stroke had significantly elevated miR-19a-3p expression levels compared to patients with minor stroke at the first day of IS. (AUC: 0.867, (95% CI, 0.74–0.10) p = 0.001). Conclusion: Combining different biomarkers of processes underlying IS pathophysiology might be beneficial for early diagnosis of ischemic events. Thus, we believe that in the future circulating biomarkers might be used in the prehospital phase of IS. In particular, circulating plasma EVs and non-coding RNAs including miRNAs are interesting candidates as bearers of circulating biomarkers due to their high stability in the blood and making them highly relevant biomarkers for IS diagnostics. Full article

(This article belongs to the Special Issue Noncoding RNAs in Regulatory Circuitries Underlying Neuronal Differentiation, Function and Disease)

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Review

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30 pages, 1388 KiB

Open AccessReview

Roles of Non-Coding RNA in Alzheimer’s Disease Pathophysiology

by Edward O. Olufunmilayo and R. M. Damian Holsinger

Int. J. Mol. Sci. 2023, 24(15), 12498; https://doi.org/10.3390/ijms241512498 - 6 Aug 2023

Cited by 5 | Viewed by 2434

Abstract

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that is accompanied by deficits in memory and cognitive functions. The disease is pathologically characterised by the accumulation and aggregation of an extracellular peptide referred to as amyloid-β (Aβ) in the form of amyloid plaques and the intracellular aggregation of a hyperphosphorelated protein tau in the form of neurofibrillary tangles (NFTs) that cause neuroinflammation, synaptic dysfunction, and oxidative stress. The search for pathomechanisms leading to disease onset and progression has identified many key players that include genetic, epigenetic, behavioural, and environmental factors, which lend support to the fact that this is a multi-faceted disease where failure in various systems contributes to disease onset and progression. Although the vast majority of individuals present with the sporadic (non-genetic) form of the disease, dysfunctions in numerous protein-coding and non-coding genes have been implicated in mechanisms contributing to the disease. Recent studies have provided strong evidence for the association of non-coding RNAs (ncRNAs) with AD. In this review, we highlight the current findings on changes observed in circular RNA (circRNA), microRNA (miRNA), short interfering RNA (siRNA), piwi-interacting RNA (piRNA), and long non-coding RNA (lncRNA) in AD. Variations in these ncRNAs could potentially serve as biomarkers or therapeutic targets for the diagnosis and treatment of Alzheimer’s disease. We also discuss the results of studies that have targeted these ncRNAs in cellular and animal models of AD with a view for translating these findings into therapies for Alzheimer’s disease. Full article

(This article belongs to the Special Issue Noncoding RNAs in Regulatory Circuitries Underlying Neuronal Differentiation, Function and Disease)

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20 pages, 1907 KiB

Open AccessReview

MicroRNAs in the Mouse Developing Retina

by Jorge Navarro-Calvo, Gema Esquiva, Violeta Gómez-Vicente and Luis M. Valor

Int. J. Mol. Sci. 2023, 24(3), 2992; https://doi.org/10.3390/ijms24032992 - 3 Feb 2023

Cited by 1 | Viewed by 2988

Abstract

The retina is among the highest organized tissues of the central nervous system. To achieve such organization, a finely tuned regulation of developmental processes is required to form the retinal layers that contain the specialized neurons and supporting glial cells to allow precise phototransduction. MicroRNAs are a class of small RNAs with undoubtful roles in fundamental biological processes, including neurodevelopment of the brain and the retina. This review provides a short overview of the most important findings regarding microRNAs in the regulation of retinal development, from the developmental-dependent rearrangement of the microRNA expression program to the key roles of particular microRNAs in the differentiation and maintenance of retinal cell subtypes. Full article

(This article belongs to the Special Issue Noncoding RNAs in Regulatory Circuitries Underlying Neuronal Differentiation, Function and Disease)

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