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Free Radical Biology & Medicine Nov 2023Physical Exercise (EXR) has been shown to have numerous beneficial effects on various systems in the human body. It leads to a decrease in the risk of mortality from... (Review)
Review
Physical Exercise (EXR) has been shown to have numerous beneficial effects on various systems in the human body. It leads to a decrease in the risk of mortality from chronic diseases, such as cardiovascular disease, cancer, metabolic and central nervous system disorders. EXR results in improving cardiovascular fitness, cognitive function, immune activity, endocrine action, and musculoskeletal health. These positive effects make EXR a valuable intervention for promoting overall health and well-being in individuals of all ages. These beneficial effects are partially mediated by the role of the regular EXR in the adaptation to redox homeostasis counteracting the sudden increase of ROS, the hallmark of many chronic diseases. EXR can trigger the release of numerous humoral factors, e.g. protein, microRNA (miRs), and DNA, that can be shuttled as cargo of Extracellular vesicles (EVs). EVs show different cargo modification after oxidative stress stimuli as well as after EXR. In this review, we aim to highlight the main studies on the role of EVs released during EXR and oxidative stress conditions in enhancing the antioxidant enzymes pathway and in the decrease of oxidative stress environment mediated by their cargo.
Topics: Humans; Oxidative Stress; Extracellular Vesicles; Exercise; MicroRNAs; Chronic Disease
PubMed: 37739138
DOI: 10.1016/j.freeradbiomed.2023.09.021 -
Nanoscale Aug 2023Bone loss is prevalent in clinical pathological phenomena such as osteoporosis, which is characterized by decreased osteoblast function and number, increased osteoclast... (Review)
Review
Bone loss is prevalent in clinical pathological phenomena such as osteoporosis, which is characterized by decreased osteoblast function and number, increased osteoclast activity, and imbalanced bone homeostasis. However, current treatment strategies for bone diseases are limited. Regulated cell death (RCD) is a programmed cell death pattern activated by the expression of specific genes in response to environmental changes. Various studies have shown that RCD is closely associated with bone diseases, and manipulating the death fate of osteoblasts could contribute to effective bone treatment. Recently, microRNA-targeting therapy drugs have emerged as a potential solution because of their precise targeting, powerful curative effect, and limited side effects. Nevertheless, their clinical application is limited by their inherent instability, easy enzymatic degradation, and poor membrane penetrability. To address this challenge, a self-assembling tetrahedral DNA nanostructure (TDN)-based microRNA (Tmi) delivery system has been proposed. TDN features excellent biocompatibility, cell membrane penetrability, serum stability, and modification versatility, making it an ideal nucleic acid carrier for miRNA protection and intracellular transport. Once inside cells, Tmi can dissociate and release miRNAs to manipulate key molecules in the RCD signaling pathway, thereby regulating bone homeostasis and curing diseases caused by abnormal RCD activation. In this paper, we discuss the impact of the miRNA network on the initiation and termination of four critical RCD programs in bone tissues: apoptosis, autophagy, pyroptosis, and ferroptosis. Furthermore, we present the Tmi delivery system as a miRNA drug vector. This provides insight into the clinical translation of miRNA nucleic acid drugs and the application of miRNA drugs in bone diseases.
Topics: Humans; MicroRNAs; Pharmaceutical Preparations; Osteoclasts; Bone and Bones; Bone Diseases
PubMed: 37482769
DOI: 10.1039/d3nr02318d -
Seminars in Cell & Developmental Biology Sep 2023Viruses have evolved a multitude of mechanisms to combat barriers to productive infection in the host cell. Virally-encoded miRNAs are one such means to regulate host... (Review)
Review
Viruses have evolved a multitude of mechanisms to combat barriers to productive infection in the host cell. Virally-encoded miRNAs are one such means to regulate host gene expression in ways that benefit the virus lifecycle. miRNAs are small non-coding RNAs that regulate protein expression but do not trigger the adaptive immune response, making them powerful tools encoded by viruses to regulate cellular processes. Diverse viruses encode for miRNAs but little sequence homology exists between miRNAs of different viral species. Despite this, common cellular pathways are targeted for regulation, including apoptosis, immune evasion, cell growth and differentiation. Herein we will highlight the viruses that encode miRNAs and provide mechanistic insight into how viral miRNAs aid in lytic and latent infection by targeting common cellular processes. We also highlight how viral miRNAs can mimic host cell miRNAs as well as how viral miRNAs have evolved to regulate host miRNA expression. These studies dispel the myth that viral miRNAs are subtle regulators of gene expression, and highlight the critical importance of viral miRNAs to the virus lifecycle.
Topics: MicroRNAs; Viruses; Cell Differentiation; Protein Processing, Post-Translational; Gene Expression; Gene Expression Regulation, Viral; Gene Expression Regulation
PubMed: 36463091
DOI: 10.1016/j.semcdb.2022.11.007 -
Biology Open Dec 2023MicroRNAs (miRNAs) are a class of noncoding RNAs that regulate gene expression. An important step in miRNA biogenesis occurs when primary miRNAs are bound and cleaved by...
MicroRNAs (miRNAs) are a class of noncoding RNAs that regulate gene expression. An important step in miRNA biogenesis occurs when primary miRNAs are bound and cleaved by the microprocessor to generate precursor miRNAs. Regulation at this step is essential and one such regulator includes m6A RNA methylation, an RNA modification found on primary miRNAs that is installed by METTL3 and bound by hnRNPA2B1. Our lab has recently discovered that the Cajal body marker protein coilin also participates in miRNA biogenesis and hypothesized that coilin may be influencing miRNA biogenesis through m6A RNA methylation. Here we report that coilin suppression reduces m6A on primary Let7a and miR-21. We also found that coilin suppression reduced the protein expression of hnRNPA2B1 and METTL3. We observed an interaction between coilin and ectopically expressed METTL3 and found that coilin suppression reduced the nucleoplasmic portion of METTL3 and blunted ectopic METTL3 phosphorylation. Finally, coilin suppression disrupted the greater METTL3 complex with cofactors METTL14 and WTAP. Collectively, our work has uncovered a role for coilin in mediating m6A RNA methylation and provides an avenue by which coilin participates in miRNA biogenesis.
Topics: Methylation; Phosphorylation; MicroRNAs; Cell Nucleus
PubMed: 38050869
DOI: 10.1242/bio.060116 -
Genes Jul 2023MicroRNAs (miRNAs), small non-coding RNA molecules, regulate a wide range of critical biological processes, such as proliferation, cell cycle progression,... (Review)
Review
MicroRNAs (miRNAs), small non-coding RNA molecules, regulate a wide range of critical biological processes, such as proliferation, cell cycle progression, differentiation, survival, and apoptosis, in many cell types. The regulatory functions of miRNAs in embryogenesis and stem cell properties have been extensively investigated since the early years of miRNA discovery. In this review, we will compare and discuss the impact of stem-cell-specific miRNA clusters on the maintenance and regulation of early embryonic development, pluripotency, and self-renewal of embryonic stem cells, particularly in vertebrates.
Topics: Animals; MicroRNAs; Pluripotent Stem Cells; Embryonic Stem Cells; Cell Differentiation; Vertebrates
PubMed: 37510338
DOI: 10.3390/genes14071434 -
Biosensors & Bioelectronics Nov 2023MicroRNAs (miRNAs) have emerged as important biomarkers in biomedicine and bioimaging due to their roles in various physiological and pathological processes. Real-time... (Review)
Review
MicroRNAs (miRNAs) have emerged as important biomarkers in biomedicine and bioimaging due to their roles in various physiological and pathological processes. Real-time and in situ monitoring of dynamic fluctuation of miRNAs in living cells is crucial for understanding these processes. However, current miRNA imaging probes still have some limitations, including the lack of effective amplification methods for low abundance miRNAs bioanalysis and uncontrollable activation, leading to background signals and potential false-positive results. Therefore, researchers have been integrating activatable devices with miRNA amplification techniques to design stimuli-responsive nanoprobes for "on-demand" and precise imaging of miRNAs in living cells. In this review, we summarize recent advances of stimuli-responsive probes for the amplification-based imaging of miRNAs in living cells and discuss the future challenges and opportunities in this field, aiming to provide valuable insights for accurate disease diagnosis and monitoring.
Topics: Humans; MicroRNAs; Gene Amplification; Cell Survival; Adenosine Triphosphate; Hydrogen-Ion Concentration
PubMed: 37619479
DOI: 10.1016/j.bios.2023.115584 -
Nucleic Acids Research Jul 2023DIANA-miRPath is an online miRNA analysis platform harnessing predicted or experimentally supported miRNA interactions towards the exploration of combined miRNA effects....
DIANA-miRPath is an online miRNA analysis platform harnessing predicted or experimentally supported miRNA interactions towards the exploration of combined miRNA effects. In its latest version (v4.0, http://www.microrna.gr/miRPathv4), DIANA-miRPath breaks new ground by introducing the capacity to tailor its target-based miRNA functional analysis engine to specific biological and/or experimental contexts. Via a redesigned modular interface with rich interaction, annotation and parameterization options, users can now perform enrichment analysis on Gene Ontology (GO) terms, KEGG and REACTOME pathways, sets from Molecular Signatures Database (MSigDB) and PFAM. Included miRNA interaction sets are derived from state-of-the-art resources of experimentally supported (DIANA-TarBase v8.0, miRTarBase and microCLIP cell-type-specific interactions) or from in silico miRNA-target interactions (updated DIANA-microT-CDS and TargetScan predictions). Bulk and single-cell expression datasets from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression project (GTEx) and adult/fetal single-cell atlases are integrated and can be used to assess the expression of enriched term components across a wide range of states. A discrete module enabling enrichment analyses using CRISPR knock-out screen datasets enables the detection of selected miRNAs with potentially crucial roles within conditions under study. Notably, the option to upload custom interaction, term, expression and screen sets further expands the versatility of miRPath webserver.
Topics: Cell Communication; Databases, Chemical; MicroRNAs; Software
PubMed: 37260078
DOI: 10.1093/nar/gkad431 -
Cellular and Molecular Neurobiology Oct 2023Migraine is a common primary headache disorder, affecting about 14% of the population. Importantly, it was indicated as the second cause of disability globally and the... (Review)
Review
Migraine is a common primary headache disorder, affecting about 14% of the population. Importantly, it was indicated as the second cause of disability globally and the leading cause among young women. Despite the widespread prevalence, migraine remains underdiagnosed and undertreated. The possible solution may be microRNAs-small, non-coding molecules. Until now, multiple studies have shown the great value of microRNA in both the diagnosis and treatment of different human diseases. Furthermore, a significant role in neurological disorders has been suggested. Little research regarding the utility of microRNA in migraine has been conducted, however, the results so far appear to be promising. We performed an electronic article search through PubMed and Embase Database to further explore the topic. After the analysis, according to PRISMA 2020 guidelines, we included 21 studies. The dysregulation was observed in migraine in general, as well as in different types and phases; thus, miRNAs emerge as promising diagnostic biomarkers. Additionally, some studies showed the influence of the intervention with miRNA levels on neuroinflammation and the expression of peptides, which are crucial in migraine pathogenesis. This review aims to summarize the current knowledge about the role of miRNAs in migraine and encourage to further research in this field.Kindly check and confirm the edit made in the title.I checked and confirm.
Topics: Humans; Female; MicroRNAs; Migraine Disorders
PubMed: 37432603
DOI: 10.1007/s10571-023-01387-9 -
Cellular Signalling Feb 2024This study delves into the role of FBLN5 in pelvic organ prolapse (POP) and its molecular mechanisms, focusing on the FOSL1/miR-222/MEIS1/COL3A1 axis. Gene relationships...
This study delves into the role of FBLN5 in pelvic organ prolapse (POP) and its molecular mechanisms, focusing on the FOSL1/miR-222/MEIS1/COL3A1 axis. Gene relationships linked to POP were confirmed using bioinformatics databases like GEO and StarBase. Primary human uterosacral ligament fibroblasts (hUSLF) were extracted and subjected to mechanical stretching. Cellular cytoskeletal changes were examined via phalloidin staining, intracellular ROS levels with a ROS kit, cell apoptosis through flow cytometry, and cell senescence using β-galactosidase staining. FBLN5's downstream targets were identified, and the interaction between FOSL1 and miR-222 and miR-222 and MEIS1 were validated using assays. In rat models, the role of FBLN5 in POP was assessed using bladder pressure tests. Results indicated diminished FBLN5 expression in uterine prolapse. Enhanced FBLN5 countered mechanical damage in hUSLF cells by downregulating FOSL1. FOSL1 augmented miR-222, inhibiting MEIS1, which subsequently fostered COL3A1 transcription. In rat models, the absence of FBLN5 exacerbated POP by influencing the FOSL1/miR-222/MEIS1/COL3A1 pathway. FBLN5's protective role likely involves regulating the above axis and boosting COL3A1 expression. Further research is needed to validate the effectiveness and safety of this mechanism in human patients and to propose potential new treatment options.
Topics: Female; Humans; Rats; Animals; Reactive Oxygen Species; Pelvic Organ Prolapse; MicroRNAs; Collagen Type III; Extracellular Matrix Proteins
PubMed: 38056607
DOI: 10.1016/j.cellsig.2023.111000 -
Gene Oct 2023Recurrent miscarriage (RM) is a complex reproductive medicine disease that affects many families. The cause of RM is unclear at this time; however, lifestyle and genetic... (Review)
Review
Recurrent miscarriage (RM) is a complex reproductive medicine disease that affects many families. The cause of RM is unclear at this time; however, lifestyle and genetic variables may influence the process. The slight alteration in miRNA expression has enormous consequences for a variety of difficulties, one of which may be RM. The target of this systematic study was to provide a framework of the dysregulated miRNAs in RM. The Prisma guidelines were applied to perform current systematic review pertaining to articles in the seven databases. Thirty-nine papers out of 245 received fulfilled all inclusion requirements. From all the mentioned miRNAs, 40 were up-regulated (65.57 %), whereas 21 were down-regulated (34.43 %). These dysregulated miRNAs contributed to the pathophysiology of RM by influencing key pathways and processes such as apoptosis, angiogenesis, epithelial-mesenchymal transition, and the immune system. Understanding the dysregulation of miRNAs, as well as the pathways and processes that engage these miRNAs and impact disease pathogenesis, may aid in clarifying the unknown underlying mechanisms of RM and the development of novel molecular therapeutic targets and medical domains.
Topics: Female; Humans; MicroRNAs; Abortion, Habitual; Immune System
PubMed: 37543220
DOI: 10.1016/j.gene.2023.147689