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Biomolecules May 2023In this study, we conducted a systematic review and meta-analysis to summarize and evaluate the global research potential of different circulating miRNAs as an early... (Meta-Analysis)
Meta-Analysis Review
In this study, we conducted a systematic review and meta-analysis to summarize and evaluate the global research potential of different circulating miRNAs as an early diagnostic biomarker for OC. A systematic literature search for relevant studies was conducted in June 2020 and followed up in November 2021. The search was conducted in English databases (PubMed, ScienceDirect). The primary search resulted in a total of 1887 articles, which were screened according to the prior established inclusion and exclusion criteria. We identified 44 relevant studies, of which 22 were eligible for the quantitative meta-analysis. Statistical analysis was performed using the Meta-package in Rstudio. Standardized mean differences (SMD) of relative levels between control subjects and OC patients were used to evaluate the differential expression. All studies were quality evaluated using a Newcastle-Ottawa Scale. Based on the meta-analysis, nine miRNAs were identified as dysregulated in OC patients compared to controls. Nine were upregulated in OC patients compared to controls (miR-21, -125, -141, -145, -205, -328, -200a, -200b, -200c). Furthermore, miR-26, -93, -106 and -200a were analyzed, but did not present an overall significant difference between OC patients and controls. These observations should be considered when performing future studies of circulating miRNAs in relation to OC: sufficient size of clinical cohorts, development of consensus guidelines for circulating miRNA measurements, and coverage of previously reported miRNAs.
Topics: Humans; Female; Circulating MicroRNA; Biomarkers, Tumor; Ovarian Neoplasms; MicroRNAs; Early Diagnosis
PubMed: 37238740
DOI: 10.3390/biom13050871 -
Brain Research Bulletin Apr 2020MicroRNAs (miRNAs) plays an important role in the human brain from the embryonic period to adulthood. In this sense, they influence the development of neural stem cells... (Review)
Review
MicroRNAs (miRNAs) plays an important role in the human brain from the embryonic period to adulthood. In this sense, they influence the development of neural stem cells (NSCs), regulating cellular differentiation and survival. Therefore, due to the importance of better comprehending the regulation of miRNAs in NSCs differentiation and the lack of studies that show the panorama of miRNAs and their signaling pathways studied until now we aimed to systematically review the literature to identify which miRNAs are currently being associated with neuronal differentiation and using bioinformatics analysis to identify their related pathways. A search was carried out in the following databases: Scientific Electronic Library Online (Scielo), National Library of Medicine National Institutes of Health (PubMed), Scopus, Web of Science and Science Direct, using the descriptors "(microRNA [MeSH])" and "(neurogenesis [MeSH])". From the articles found, two independent and previously calibrated reviewers, using the EndNote X7 (Thomson Reuters, New York, NY, US), selected those that concern miRNA in the development of NSCs, based on in vitro studies. After, bioinformatic analysis was performed using the software DIANA Tools, mirPath v.3. Subsequently, data was tabulated, analyzed and interpreted. Among the 106 miRNAs cited by included studies, 55 were up-regulated and 47 were down-regulated. The bioinformatics analysis revealed that among the up-regulated miRNAs there were 24 total and 6 union pathways, and 3 presented a statistically significant difference (p ≤ 0.05). Among the down-regulated miRNAs, 46 total and 13 union pathways were found, with 7 presenting a significant difference (p ≤ 0.05). The miR-125a-5p, miR-423-5p, miR-320 were the most frequently found miRNAs in the pathways determined by bioinformatics. In this study a panel of altered miRNAs in neuronal differentiation was created with their related pathways, which could be a step towards understanding the complex network of miRNAs in neuronal differentiation.
Topics: Animals; Cell Differentiation; Computational Biology; Gene Expression Profiling; Humans; MicroRNAs; Neural Stem Cells; Neurogenesis
PubMed: 31945407
DOI: 10.1016/j.brainresbull.2020.01.009 -
Bioscience Reports May 2022The relationship between microRNA-21 (miRNA-21) and pathogenesis of lung cancer is a considerable focus of research interest. However, to our knowledge, no in-depth... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The relationship between microRNA-21 (miRNA-21) and pathogenesis of lung cancer is a considerable focus of research interest. However, to our knowledge, no in-depth meta-analyses based on existing evidence to ascertain the value of miRNA-21 in diagnosis and clinical prognosis of lung cancer have been documented.
METHODS
We comprehensively searched all the literature pertaining to 'miRNA-21' and 'lung cancer' from four databases from the period of inception of each database until May 2020. Using specific inclusion and exclusion criteria, the literature for inclusion was identified and the necessary data extracted.
RESULTS
In total, 46 articles were included in the meta-analysis, among which 31 focused on diagnostic value and 15 on prognostic value. Combined sensitivity (SEN) of miRNA-21 in diagnosis of lung cancer was 0.77 (95% confidence interval (CI): 0.72-0.81), specificity (SPE) was 0.86 (95% CI: 0.80-0.90), diagnostic odds ratio (DOR) was (95% CI: 12-33), and area under the SROC curve (AUC) was 0.87 (95% CI: 0.84-0.90). No significant correlations were observed between abnormal expression of miRNA-21 and gender, smoking habits, pathological type and clinical stage of lung cancer (P>0.05). In terms of overall survival (OS), univariate analysis (hazards ratio (HR) = 1.49, 95% CI: 1.22-1.82) revealed high expression of miRNA-21 as an influencing factor for lung cancer. MiRNA-21 was confirmed as an independent risk factor for poor prognosis in multivariate analysis (HR = 1.65, 95% CI: 1.24-2.19).
CONCLUSION
MiRNA-21 has potential clinical value in the diagnosis and prognosis of lung cancer and may serve as an effective diagnostic marker and therapeutic target in the future.
Topics: Biomarkers, Tumor; Humans; Lung Neoplasms; MicroRNAs; Prognosis; Proportional Hazards Models
PubMed: 35441676
DOI: 10.1042/BSR20211653 -
International Journal of Molecular... Dec 2022Stroke accounts for the second leading cause of death and a major cause of disability, with limited therapeutic strategy in both the acute and chronic phases.... (Meta-Analysis)
Meta-Analysis Review
Stroke accounts for the second leading cause of death and a major cause of disability, with limited therapeutic strategy in both the acute and chronic phases. Blood-based biomarkers are intensively researched and widely recognized as useful tools to predict the prognoses of patients confronted with therapeutically limited diseases. We performed a systematic review of the circulating biomarkers in IS patients with prognostic value, with a focus on microRNAs and exosomes as predictive biomarkers of motor and cognitive recovery. We identified 63 studies, totalizing 72 circulating biomarkers with prognostic value in stroke recovery, as follows: 68 miRNAs and exosomal-miRNAs being identified as predictive for motor recovery after stroke, and seven biomarkers being predictive for cognitive recovery. Twelve meta-analyses were performed using effect sizes (random-effects and fixed-effects model). The most significant correlation findings obtained after pooling were with miR-21, miR-29b, miR-125b-5p, miR-126, and miR-335. We identified several miRNAs that were correlated with clinical outcomes of stroke severity and recovery after ischemic stroke, providing predictive information on motor and cognitive recovery. Based on the current state of research, we identified serum miR-9 and neutrophil miR-29b as the most promising biomarkers for in-depth follow-up studies, followed by serum miR-124 and plasma miR-125b.
Topics: Humans; Circulating MicroRNA; Ischemic Stroke; MicroRNAs; Stroke; Biomarkers; Exosomes
PubMed: 36613694
DOI: 10.3390/ijms24010251 -
Journal of Sport and Health Science May 2024Regular physical exercise has been recognized as a potent modulator of immune function, with its effects including enhanced immune surveillance, reduced inflammation,... (Review)
Review
Regular physical exercise has been recognized as a potent modulator of immune function, with its effects including enhanced immune surveillance, reduced inflammation, and improved overall health. While strong evidence exists that physical exercise affects the specific expression and activity of non-coding RNAs (ncRNAs) also involved in immune system regulation, heterogeneity in individual study designs and analyzed exercise protocols exists, and a condensed list of functional, exercise-dependent ncRNAs with known targets in the immune system is missing from the literature. A systematic review and qualitative analysis was used to identify and categorize ncRNAs participating in immune modulation by physical exercise. Two combined approaches were used: (a) a systematic literature search for "ncRNA and exercise immunology", (b) and a database search for microRNAs (miRNAs) (miRTarBase and DIANA-Tarbase v8) aligned with known target genes in the immune system based on the Reactome database, combined with a systematic literature search for "ncRNA and exercise". Literature searches were based on PubMed, Web of Science, and SPORTDiscus; and miRNA databases were filtered for targets validated by in vitro experimental data. Studies were eligible if they reported on exercise-based interventions in healthy humans. After duplicate removal, 95 studies were included reporting on 164 miRNAs, which were used for the qualitative synthesis. Six studies reporting on long-noncoding RNAs (lncRNAs) or circular RNAs were also identified. Results were analyzed using ordering tables that included exercise modality (endurance/resistance exercise), acute or chronic interventions, as well as the consistency in reported change between studies. Evaluation criteria were defined as "validated" with 100% of ≥3 independent studies showing identical direction of regulation, "plausible" (≥80%), or "suggestive" (≥70%). For resistance exercise, upregulation of miR-206 was validated while downregulation of miR-133a appeared plausible. For endurance exercise, 15 miRNAs were categorized as validated, with 12 miRNAs being consistently elevated and 3 miRNAs being downregulated, most of them after acute exercise training. In conclusion, our approach provides evidence that miRNAs play a major role in exercise-induced effects on the innate and adaptive immune system by targeting different pathways affecting immune cell distribution, function, and trafficking as well as production of (anti-)inflammatory cytokines. miRNAs miR-15, miR-29c, miR-30a, miR-142/3, miR-181a, and miR-338 emerged as key players in mediating the immunomodulatory effects of exercise predominantly after acute bouts of endurance exercise.
Topics: Humans; Exercise; MicroRNAs; RNA, Untranslated; Immune System
PubMed: 37925072
DOI: 10.1016/j.jshs.2023.11.001 -
Herz Dec 2022Current genetic association studies have reported conflicting results regarding the association between miRNA polymorphisms and myocardial infarction (MI) risk METHODS:... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Current genetic association studies have reported conflicting results regarding the association between miRNA polymorphisms and myocardial infarction (MI) risk METHODS: Relevant studies were retrieved from the PubMed, EMBASE, ISI Web of Science, and Scopus databases. Eligible studies determining the association between miRNA polymorphisms and MI susceptibility were included and a meta-analysis was performed to quantify the associations between miRNA polymorphisms and MI risk.
RESULTS
A total of eight studies with 2507 MI patients and 3796 healthy controls were included, dealing with nine miRNA genes containing 11 different loci, including miR-149 (rs71428439 and rs2292832), miR-126 (rs4636297 and rs1140713), miR-146a (rs2910164), miR-218 (rs11134527), miR-196a2 (rs11614913), miR-499 (rs3746444), miR-27a (rs895819), miR-26a‑1 (rs7372209), and miR-100 (rs1834306). miR-146a rs2910164 and miR-499 rs3746444 were determined to have a significant association with MI susceptibility, a finding that was supported by the meta-analysis (rs2910164: GG/CC, odds ratio [OR]: 1.40, 95% confidence interval [95% CI]: 1.05-1.74, p < 0.001; rs3746444: AA + AG/GG, OR = 2.04, 95% CI: 1.37-2.70, p < 0.001). Limited or conflicting data were found for the relationship between the other miRNA polymorphisms (rs71428439, rs4636297, rs1140713, rs11134527, rs11614913, rs895819, rs7372209, rs1834306, rs2292832) and MI risk.
CONCLUSION
There was a significant association between rs2910164 and rs3746444 and MI susceptibility. Further studies are required to investigate the role of miRNA polymorphisms in MI risk.
Topics: Humans; Genetic Association Studies; Genetic Predisposition to Disease; MicroRNAs; Myocardial Infarction; Polymorphism, Single Nucleotide
PubMed: 34878577
DOI: 10.1007/s00059-021-05086-3 -
Experimental Biology and Medicine... Jan 2020Association between microRNA (miRNA) expression signatures and atrial fibrillation has been evaluated with inconsistent findings in different studies. This study aims to... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Association between microRNA (miRNA) expression signatures and atrial fibrillation has been evaluated with inconsistent findings in different studies. This study aims to identify miRNAs that actually play vital role in pathophysiological process of atrial fibrillation and explore miRNA-targeted genes and the involved pathways. Relevant studies were retrieved from the electronic databases of Embase, Medline, and Cochrane Library to determine the miRNA expression profiles between atrial fibrillation subjects and non-atrial fibrillation controls. Robustness of results was assessed using sensitivity analysis. Subgroup analyses were performed based on species, miRNA detection method, sample source, and ethnicity. Quality assessment of studies was independently conducted according to QUADAS-2. Bioinformatics analysis was applied to explore the potential genes and pathways associated with atrial fibrillation, which were targeted by differentially expressed miRNAs. Form of pooled results was shown as log10 odds ratios (logORs) with 95% confidence intervals (CI), and random-effects model was used. In total, 40 articles involving 283 differentially expressed miRNAs were reported. And 51 significantly dysregulated miRNAs were identified in consistent direction, with 22 upregulated and 29 downregulated. Among above-mentioned miRNAs, miR-223-3p (logOR 6.473; P < 0.001) was the most upregulated, while miR-1-5p (logOR 7.290; P < 0.001) was the most downregulated. Subgroup analysis confirmed 53 significantly dysregulated miRNAs (21 upregulated and 32 downregulated) in cardiac tissue, with miRNA-1-5p and miRNA-223-3p being the most upregulated and downregulated miRNAs, respectively. Additionally, miR-328 and miR-1-5p were highly blood-specific, and miR-133 was animal-specific. In the detection method sub-groups, miRNA-29b and miRNA-223-3p were differentially expressed consistently. Four miRNAs, including miRNA-223-3p, miRNA-21, miRNA-328, and miRNA-1-5p, were consistently dysregulated in both Asian and non-Asian. Results of sensitivity analysis showed that 47 out of 51 (92.16%) miRNAs were dysregulated consistently. Totally, 51 consistently dysregulated miRNAs associated with atrial fibrillation were confirmed in this study. Five important miRNAs, including miR-29b, miR-328, miR-1-5p, miR-21, and miR-223-3p may act as potential biomarkers for atrial fibrillation.
IMPACT STATEMENT
Atrial fibrillation (AF) is considered as the most common arrhythmia, and it subsequently causes serious complications including thrombosis and heart failure that increase the social burden. The definite mechanisms underlying AF pathogenesis remain complicated and unclear. Many studies attempted to discover the transcriptomic changes using microarray technologies, and the present studies for this hot topic have assessed individual miRNAs profiles for AF. However, results of different articles are controversial and not each reported miRNA is actually associated with the pathogenesis of AF. The present systematic review and meta-analysis identified that 51 consistently dysregulated miRNAs were associated with AF. Of these miRNAs, five miRNAs (miRNA-1-5p, miRNA-328, miRNA-29b, miRNA-21, and miRNA-223-3p) may act as novel biomarkers for AF. The findings could offer a better description of the biological characteristics of miRNAs, meanwhile might serve as new target for the intervention and monitoring AF in future studies.
Topics: Animals; Atrial Fibrillation; Computational Biology; Down-Regulation; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; Humans; MicroRNAs; Up-Regulation
PubMed: 31766887
DOI: 10.1177/1535370219890303 -
Journal of Cachexia, Sarcopenia and... Feb 2022Sarcopenic obesity is a distinct condition of sarcopenia in the context of obesity, with the cumulative health risks of both phenotypes. Differential expression of... (Review)
Review
Sarcopenic obesity is a distinct condition of sarcopenia in the context of obesity, with the cumulative health risks of both phenotypes. Differential expression of microRNAs (miRNAs) has been reported separately in people with obesity and sarcopenia and may play a role in the pathogenesis of sarcopenic obesity. However, this has not been explored to date. This study aimed to identify differentially expressed miRNAs reported in serum, plasma, and skeletal muscle of people with obesity and sarcopenia and whether there are any commonalities between these conditions. We performed a systematic review on Embase and MEDLINE (PROSPERO, CRD42020224486) for differentially expressed miRNAs (fold change >1.5 or P-value <0.05) in (i) sarcopenia or frailty and (ii) obesity or metabolic syndrome. The functions and targets of miRNAs commonly changed in both conditions, in the same direction, were searched using PubMed. Following deduplication, 247 obesity and 42 sarcopenia studies were identified for full-text screening. Screening identified 36 obesity and 6 sarcopenia studies for final inclusion. A total of 351 miRNAs were identified in obesity and 157 in sarcopenia. Fifty-five miRNAs were identified in both obesity and sarcopenia-by sample type, 48 were found in plasma and one each in serum and skeletal muscle. Twenty-four miRNAs were identified from 10 of the included studies as commonly changed in the same direction (22 in plasma and one each in serum and skeletal muscle) in obesity and sarcopenia. The majority of miRNA-validated targets identified in the literature search were members of the phosphoinositide 3-kinase/protein kinase B and transforming growth factor-β signalling pathways. The most common targets identified were insulin-like growth factor 1 (miR-424-5p, miR-483-3p, and miR-18b-5p) and members of the SMAD family (miR-483-3p, miR-92a-3p, and miR-424-5p). The majority of commonly changed miRNAs were involved in protein homeostasis, mitochondrial dynamics, determination of muscle fibre type, insulin resistance, and adipogenesis. Twenty-four miRNAs were identified as commonly dysregulated in obesity and sarcopenia with functions and targets implicated in the pathogenesis of sarcopenic obesity. Given the adverse health outcomes associated with sarcopenic obesity, understanding the pathogenesis underlying this phenotype has the potential to lead to effective screening, monitoring, or treatment strategies. Further research is now required to confirm whether these miRNAs are differentially expressed in older adults with sarcopenic obesity.
Topics: Adipogenesis; Aged; Humans; MicroRNAs; Obesity; Phosphatidylinositol 3-Kinases; Sarcopenia
PubMed: 34984856
DOI: 10.1002/jcsm.12878 -
Frontiers in Endocrinology 2022Gestational diabetes (GDM) is associated with increased risk for preterm birth and related complications for both the pregnant person and newborn. Changes in gene...
PURPOSE
Gestational diabetes (GDM) is associated with increased risk for preterm birth and related complications for both the pregnant person and newborn. Changes in gene expression have the potential to characterize complex interactions between genetic and behavioral/environmental risk factors for GDM. Our goal was to summarize the state of the science about changes in gene expression and GDM.
DESIGN
The systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
METHODS
PubMed articles about humans, in English, from any date were included if they described mRNA transcriptome or microRNA findings from blood samples in adults with GDM compared with adults without GDM.
RESULTS
Sixteen articles were found representing 1355 adults (n=674 with GDM, n=681 controls) from 12 countries. Three studies reported transcriptome results and thirteen reported microRNA findings. Identified pathways described various aspects of diabetes pathogenesis, including glucose and insulin signaling, regulation, and transport; natural killer cell mediated cytotoxicity; and fatty acid biosynthesis and metabolism. Studies described 135 unique miRNAs that were associated with GDM, of which eight (miR-16-5p, miR-17-5p, miR-20a-5p, miR-29a-3p, miR-195-5p, miR-222-3p, miR-210-3p, and miR-342-3p) were described in 2 or more studies. Findings suggest that miRNA levels vary based on the time in pregnancy when GDM develops, the time point at which they were measured, sex assigned at birth of the offspring, and both the pre-pregnancy and gestational body mass index of the pregnant person.
CONCLUSIONS
The mRNA, miRNA, gene targets, and pathways identified in this review contribute to our understanding of GDM pathogenesis; however, further research is warranted to validate previous findings. In particular, longitudinal repeated-measures designs are needed that control for participant characteristics (e.g., weight), use standardized data collection methods and analysis tools, and are sufficiently powered to detect differences between subgroups. Findings may be used to improve early diagnosis, prevention, medication choice and/or clinical treatment of patients with GDM.
Topics: Adult; Female; Humans; Pregnancy; Diabetes, Gestational; MicroRNAs; Premature Birth; Signal Transduction; Transcriptome
PubMed: 36704034
DOI: 10.3389/fendo.2022.971354 -
Clinical and Translational Medicine Jan 2023Approximately 10% of all bone fractures result in delayed fracture healing or non-union; thus, the identification of biomarkers and prognostic factors is of great... (Review)
Review
BACKGROUND
Approximately 10% of all bone fractures result in delayed fracture healing or non-union; thus, the identification of biomarkers and prognostic factors is of great clinical interest. MicroRNAs (miRNAs) are known to be involved in the regulation of the bone healing process and may serve as functional markers for fracture healing.
AIMS AND METHODS
This systematic review aimed to identify common miRNAs involved in fracture healing or non-union fractures using a qualitative approach. A systematic literature search was performed with the keywords 'miRNA and fracture healing' and 'miRNA and non-union fracture'. Any original article investigating miRNAs in fracture healing or non-union fractures was screened. Eventually, 82 studies were included in the qualitative analysis for 'miRNA and fracture healing', while 19 were selected for the 'miRNA and fracture non-union' category.
RESULTS AND CONCLUSIONS
Out of 151 miRNAs, miR-21, miR-140 and miR-214 were the most investigated miRNAs in fracture healing in general. miR-31-5p, miR-221 and miR-451-5p were identified to be regulated specifically in non-union fractures. Large heterogeneity was detected between studies investigating the role of miRNAs in fracture healing or non-union in terms of patient population, sample types and models used. Nonetheless, our approach identified some miRNAs with the potential to serve as biomarkers for non-union fractures, including miR-31-5p, miR-221 and miR-451-5p. We provide a discussion of involved pathways and suggest on alignment of future research in the field.
Topics: Humans; MicroRNAs; Prognosis; Fracture Healing; Fractures, Bone; Biomarkers
PubMed: 36629031
DOI: 10.1002/ctm2.1161