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Ageing Research Reviews Nov 2022Modifications of RNA, collectively called the "epitranscriptome", might provide novel biomarkers and innovative targets for interventions in geroscience but are just... (Review)
Review
Modifications of RNA, collectively called the "epitranscriptome", might provide novel biomarkers and innovative targets for interventions in geroscience but are just beginning to be studied in the context of ageing and stress resistance. RNA modifications modulate gene expression by affecting translation initiation and speed, miRNA binding, RNA stability, and RNA degradation. Nonetheless, the precise underlying molecular mechanisms and physiological consequences of most alterations of the epitranscriptome are still only poorly understood. We here systematically review different types of modifications of rRNA, tRNA and mRNA, the methodology to analyze them, current challenges in the field, and human disease associations. Furthermore, we compiled evidence for a connection between individual enzymes, which install RNA modifications, and lifespan in yeast, worm and fly. We also included resistance to different stressors and competitive fitness as search criteria for genes potentially relevant to ageing. Promising candidates identified by this approach include RCM1/NSUN5, RRP8, and F33A8.4/ZCCHC4 that introduce base methylations in rRNA, the methyltransferases DNMT2 and TRM9/ALKBH8, as well as factors involved in the thiolation or A to I editing in tRNA, and finally the mA machinery for mRNA.
Topics: Aging; AlkB Homolog 8, tRNA Methyltransferase; Animals; Humans; Methyltransferases; MicroRNAs; RNA, Messenger; RNA, Ribosomal; RNA, Transfer; Saccharomyces cerevisiae
PubMed: 35908668
DOI: 10.1016/j.arr.2022.101700 -
International Journal of Molecular... Nov 2022Heart failure is defined as a clinical syndrome consisting of key symptoms and is due to a structural and/or functional alteration of the heart that results in increased... (Review)
Review
Heart failure is defined as a clinical syndrome consisting of key symptoms and is due to a structural and/or functional alteration of the heart that results in increased intracardiac pressures and/or inadequate cardiac output at rest and/or during exercise. One of the key mechanisms determining myocardial dysfunction in heart failure is oxidative stress. MicroRNAs (miRNAs, miRs) are short, endogenous, conserved, single-stranded non-coding RNAs of around 21-25 nucleotides in length that act as regulators of multiple processes. A systematic review following the PRISMA guidelines was performed on the evidence on the interplay between microRNA and oxidative stress in heart failure. A search of Pubmed, Embase, Scopus, and Scopus direct databases using the following search terms: 'heart failure' AND 'oxidative stress' AND 'microRNA' or 'heart failure' AND 'oxidative stress' AND 'miRNA' was conducted and resulted in 464 articles. Out of them, 15 full text articles were eligible for inclusion in the qualitative analysis. Multiple microRNAs are involved in the processes associated with oxidative stress leading to heart failure development including mitochondrial integrity and function, antioxidant defense, iron overload, ferroptosis, and survival pathways.
Topics: Humans; MicroRNAs; Heart Failure; Oxidative Stress; Antioxidants; Cardiomyopathies
PubMed: 36499336
DOI: 10.3390/ijms232315013 -
International Journal of Molecular... Nov 2022Plant miRNAs are powerful regulators of gene expression at the post-transcriptional level, which was repeatedly proved in several model plant species. miRNAs are... (Review)
Review
Plant miRNAs are powerful regulators of gene expression at the post-transcriptional level, which was repeatedly proved in several model plant species. miRNAs are considered to be key regulators of many developmental, homeostatic, and immune processes in plants. However, our understanding of plant miRNAs is still limited, despite the fact that an increasing number of studies have appeared. This systematic review aims to summarize our current knowledge about miRNAs in spring barley (), which is an important agronomical crop worldwide and serves as a common monocot model for studying abiotic stress responses as well. This can help us to understand the connection between plant miRNAs and (not only) abiotic stresses in general. In the end, some future perspectives and open questions are summarized.
Topics: Hordeum; MicroRNAs; Stress, Physiological; Plants; Gene Expression Regulation, Plant
PubMed: 36499082
DOI: 10.3390/ijms232314755 -
International Journal of Molecular... Jul 2023Cholesteatoma is a temporal bone disease characterized by dysfunctions of keratinocytes. MicroRNAs (miRNAs) are evolutionary conserved noncoding RNAs that regulate mRNA... (Review)
Review
Cholesteatoma is a temporal bone disease characterized by dysfunctions of keratinocytes. MicroRNAs (miRNAs) are evolutionary conserved noncoding RNAs that regulate mRNA expression. They can be packaged into exosomes and transported to target cells that can be used in the future therapy of cholesteatoma. This study aimed to collect knowledge on the role of miRNAs and exosomal miRNAs in cholesteatoma and was conducted according to the PRISMA guidelines for systematic reviews. Four databases were screened: Pubmed/MEDLINE, Web of Science, Scopus, and the Cochrane Library. The last search was run on the 6th of June 2023. We included full-text original studies written in English, which examined miRNAs in cholesteatoma. The risk of bias was assessed using the Office of Health Assessment and Translation (OHAT) Risk of Bias Rating Tool, modified for the needs of this review. We identified 118 records and included 18 articles. Analyses revealed the downregulation of exosomal miR-17 as well as miR-10a-5p, miR-125b, miR-142-5p, miR34a, miR-203a, and miR-152-5p and the overexpression of exosomal miR-106b-5p as well as miR-1297, miR-26a-5p, miR-199a, miR-508-3p, miR-21-3p, miR-584-5p, and miR-16-1-3p in cholesteatoma. The role of differentially expressed miRNAs in cholesteatoma, including cell proliferation, apoptosis, the cell cycle, differentiation, bone resorption, and the remodeling process, was confirmed, making them a potential therapeutic target in this disease.
Topics: Humans; MicroRNAs; Cholesteatoma; RNA, Untranslated; Down-Regulation; Keratinocytes; Exosomes
PubMed: 37569652
DOI: 10.3390/ijms241512277 -
Frontiers in Immunology 2022The coronavirus disease 2019 (COVID-19) pandemic has had an enormous impact on the world, affecting people's lifestyle, economy, and livelihood. Recently, with the...
The coronavirus disease 2019 (COVID-19) pandemic has had an enormous impact on the world, affecting people's lifestyle, economy, and livelihood. Recently, with the development of vaccines, the number of infected cases has decreased. Many case reports have revealed that COVID-19 may induce other serious comorbidities such as anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis. Anti-NMDA receptor encephalitis is an acute autoimmune disease that occurs more commonly in women than in men. To explore the association between COVID-19 and anti-NMDA receptor encephalitis, the microRNA (miRNA) biomarkers of COVID-19, anti-NMDA receptor encephalitis, and other related diseases from the literature are reviewed; then on the basis of these miRNA biomarkers, the relationship between COVID-19 and anti-NMDA receptor encephalitis is discussed. miRNAs are small non-coding RNAs that play important roles in cell differentiation, development, cell-cycle regulation, and apoptosis. miRNAs have been used as biological biomarkers for many diseases. The results in this study reveal that the relationship between anti-NMDA receptor encephalitis and COVID-19 infection or COVID-19 vaccination cannot be excluded; however, the risk that COVID-19 triggers the anti-NMDA receptor encephalitis is not high.
Topics: Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Biomarkers; COVID-19; COVID-19 Vaccines; Female; Humans; Male; MicroRNAs
PubMed: 35392089
DOI: 10.3389/fimmu.2022.825103 -
Wiley Interdisciplinary Reviews. RNA May 2021Addiction is a chronic and relapsing brain disorder characterized by compulsive seeking despite adverse consequences. There are both heritable and epigenetic mechanisms... (Review)
Review
Addiction is a chronic and relapsing brain disorder characterized by compulsive seeking despite adverse consequences. There are both heritable and epigenetic mechanisms underlying drug addiction. Emerging evidence suggests that non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), long non-coding RNAs, and circular RNAs regulate synaptic plasticity and related behaviors caused by substances of abuse. These ncRNAs modify gene expression and may contribute to the behavioral phenotypes of addiction. Among the ncRNAs, the most widely researched and impactful are miRNAs. The goal in this systematic review is to provide a detailed account of recent research involving the role of miRNAs in addiction. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Small Molecule-RNA Interactions RNA in Disease and Development > RNA in Disease.
Topics: Behavior, Addictive; Gene Expression; Humans; MicroRNAs; RNA, Circular; RNA, Long Noncoding; RNA, Untranslated
PubMed: 33336550
DOI: 10.1002/wrna.1637 -
EBioMedicine Jul 2023Various studies have reported cell-free RNAs (cfRNAs) as noninvasive biomarkers for detecting hepatocellular carcinoma (HCC). However, they have not been independently...
BACKGROUND
Various studies have reported cell-free RNAs (cfRNAs) as noninvasive biomarkers for detecting hepatocellular carcinoma (HCC). However, they have not been independently validated, and some results are contradictory. We provided a comprehensive evaluation of various types of cfRNA biomarkers and a full mining of the biomarker potential of new features of cfRNA.
METHODS
We first systematically reviewed reported cfRNA biomarkers and calculated dysregulated post-transcriptional events and cfRNA fragments. In 3 independent multicentre cohorts, we further selected 6 cfRNAs using RT-qPCR, built a panel called HCCMDP with AFP using machine learning, and internally and externally validated HCCMDP's performance.
FINDINGS
We identified 23 cfRNA biomarker candidates from a systematic review and analysis of 5 cfRNA-seq datasets. Notably, we defined the cfRNA domain to describe cfRNA fragments systematically. In the verification cohort (n = 183), cfRNA fragments were more likely to be verified, while circRNA and chimeric RNA candidates were neither abundant nor stable as qPCR-based biomarkers. In the algorithm development cohort (n = 287), we build and test the panel HCCMDP with 6 cfRNA markers and AFP. In the independent validation cohort (n = 171), HCCMDP can distinguish HCC patients from control groups (all: AUC = 0.925; CHB: AUC = 0.909; LC: AUC = 0.916), and performs well in distinguishing early-stage HCC patients (all: AUC = 0.936; CHB: AUC = 0.917; LC: AUC = 0.928).
INTERPRETATION
This study comprehensively evaluated full-spectrum cfRNA biomarker types for HCC detection, highlighted the cfRNA fragment as a promising biomarker type in HCC detection, and provided a panel HCCMDP.
FUNDING
National Natural Science Foundation of China, and The National Key Basic Research Program (973 program).
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; alpha-Fetoproteins; Cell-Free Nucleic Acids; Biomarkers, Tumor; ROC Curve; MicroRNAs
PubMed: 37315449
DOI: 10.1016/j.ebiom.2023.104645 -
Non-coding RNA Sep 2023Head and neck squamous cell carcinomas (HNSCCs) are often diagnosed at advanced stages, incurring significant high mortality and morbidity. Several microRNAs (miRs) have... (Review)
Review
Head and neck squamous cell carcinomas (HNSCCs) are often diagnosed at advanced stages, incurring significant high mortality and morbidity. Several microRNAs (miRs) have been identified as pivotal players in the onset and advancement of HNSCCs, operating as either oncogenes or tumor suppressors. Distinctive miR patterns identified in tumor samples, as well as in serum, plasma, or saliva, from patients have significant clinical potential for use in the diagnosis and prognosis of HNSCCs and as potential therapeutic targets. The aim of this study was to identify previous systematic reviews with meta-analysis data and clinical trials that showed the most promising miRs in HNSCCs, enclosing them into a biomolecular signature to test the prognostic value on a cohort of HNSCC patients according to The Cancer Genome Atlas (TCGA). Three electronic databases (PubMed, Scopus, and Science Direct) and one registry (the Cochrane Library) were investigated, and a combination of keywords such as "signature microRNA OR miR" AND "HNSCC OR LSCC OR OSCC OR oral cancer" were searched. In total, 15 systematic literature reviews and 76 prognostic clinical reports were identified for the study design and inclusion process. All survival index data were extracted, and the three miRs (miR-21, miR-155, and miR-375) most investigated and presenting the largest number of patients included in the studies were selected in a molecular biosignature. The difference between high and low tissue expression levels of miR-21, miR-155, and miR-375 for OS had an HR = 1.28, with 95% CI: [0.95, 1.72]. In conclusion, the current evidence suggests that miRNAs have potential prognostic value to serve as screening tools for clinical practice in HNSCC follow-up and treatment. Further large-scale cohort studies focusing on these miRNAs are recommended to verify the clinical utility of these markers individually and/or in combination.
PubMed: 37736900
DOI: 10.3390/ncrna9050054 -
International Journal of Molecular... May 2023Breast cancer continues to be the leading cause of death in women worldwide. Mammography, which is the current gold standard technique used to diagnose it, presents... (Meta-Analysis)
Meta-Analysis Review
Breast cancer continues to be the leading cause of death in women worldwide. Mammography, which is the current gold standard technique used to diagnose it, presents strong limitations in early ages where breast cancer is much more aggressive and fatal. MiRNAs present in numerous body fluids might represent a new line of research in breast cancer biomarkers, especially oncomiRNAs, known to play an important role in the suppression and development of neoplasms. The aim of this systematic review and meta-analysis was to evaluate dysregulated miRNA biomarkers and their diagnostic accuracy in breast cancer. Two independent researchers reviewed the included studies according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A protocol for this review was registered in PROSPERO with the registration number "CRD42021256338". Observational case-control-based studies analyzing concentrations of microRNAs which have been published within the last 10 years were selected, and the concentrations of miRNAs in women with breast cancer and healthy controls were analyzed. Random-effects meta-analyses of miR-155 were performed on the studies which provided enough data to calculate diagnostic odds ratios. We determined that 34 microRNAs were substantially dysregulated and could be considered biomarkers of breast cancer. Individually, miR-155 provided better diagnostic results than mammography on average. However, when several miRNAs are used to screen, forming a panel, sensitivity and specificity rates improve, and they can be associated with classic biomarkers such us CA-125 or CEA. Based on the results of our meta-analysis, miR-155 might be a promising diagnostic biomarker for this patient population.
Topics: Humans; Female; MicroRNAs; Biomarkers, Tumor; Breast Neoplasms; Breast; Sensitivity and Specificity
PubMed: 37175974
DOI: 10.3390/ijms24098270 -
Cancer Cell International Jun 2021Laryngeal carcinoma is a primary malignant tumor originating from the laryngeal mucosa, and its pathogenesis is not fully understood. It is a rare type of cancer that... (Review)
Review
BACKGROUND
Laryngeal carcinoma is a primary malignant tumor originating from the laryngeal mucosa, and its pathogenesis is not fully understood. It is a rare type of cancer that shows a downward trend in the 5-year survival rate. In clinical practice, dysregulated microRNAs are often observed in patients with laryngeal cancer. In recent years, an increasing number of studies have confirmed that the strong biomarker potential of microRNAs. We conducted a systematic review and meta-analysis to identify and highlight multiple microRNAs as biomarkers for disease prognosis in patients with laryngeal cancer.
METHODS
We actively searched the systematic reviews in PubMed, Embase, Web of Science and The Cochrane Library to select the studies that met the proposed guidelines. A total of 5307 patients with laryngeal cancer were included in this study to evaluate the association between microRNAs expression levels and patient outcomes. For overall survival in the clinical stage, a hazard ratio (HR) and corresponding 95% confidence interval (CI) are calculated to assess the effect of survival.
RESULTS
A total of 36 studies on microRNAs and laryngeal cancer recovery were included in this meta-analysis. The selected endpoints for these studies included overall survival (OS) and disease-free survival (DFS).The comorbidities of overexpression and underexpression of microRNAs were 1.13 (95% CI 1.06-1.20, P < 0.05) and 1.10 (95% CI 1.00-1.20, P < 0.05), respectively.
CONCLUSION
MiRNA-100, miRNA-155, miRNA-21, miRNA-34a, miRNA-195 and miR-let-7 are expected to be potential noninvasive and simple markers for laryngeal cancer.
PubMed: 34158050
DOI: 10.1186/s12935-021-02021-8