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International Journal of Molecular... Nov 2023The objective was to evaluate the current evidence regarding the etiology of medication-related osteonecrosis of the jaw (MRONJ). This study systematically reviewed the... (Review)
Review
The objective was to evaluate the current evidence regarding the etiology of medication-related osteonecrosis of the jaw (MRONJ). This study systematically reviewed the literature by searching PubMed, Web of Science, and ProQuest databases for genes, proteins, and microRNAs associated with MRONJ from the earliest records through April 2023. Conference abstracts, letters, review articles, non-human studies, and non-English publications were excluded. Twelve studies meeting the inclusion criteria involving exposure of human oral mucosa, blood, serum, saliva, or adjacent bone or periodontium to anti-resorptive or anti-angiogenic agents were analyzed. The Cochrane Collaboration risk assessment tool was used to assess the quality of the studies. A total of 824 differentially expressed genes/proteins (DEGs) and 22 microRNAs were extracted for further bioinformatic analysis using Cytoscape, STRING, BiNGO, cytoHubba, MCODE, and ReactomeFI software packages and web-based platforms: DIANA mirPath, OmicsNet, and miRNet tools. The analysis yielded an interactome consisting of 17 hub genes and hsa-mir-16-1, hsa-mir-21, hsa-mir-23a, hsa-mir-145, hsa-mir-186, hsa-mir-221, and hsa-mir-424. A dominance of cytokine pathways was observed in both the cluster of hub DEGs and the interactome of hub genes with dysregulated miRNAs. In conclusion, a panel of genes, miRNAs, and related pathways were found, which is a step toward understanding the complexity of the disease.
Topics: Humans; MicroRNAs; Osteonecrosis; Computational Biology; Gene Regulatory Networks
PubMed: 38069068
DOI: 10.3390/ijms242316745 -
International Journal of Molecular... Oct 2023Circulating extracellular vesicle (EV)-derived microRNAs (miRNAs) are now considered the next generation of cancer "theranostic" tools, with strong clinical relevance....
Circulating extracellular vesicle (EV)-derived microRNAs (miRNAs) are now considered the next generation of cancer "theranostic" tools, with strong clinical relevance. Although their potential in breast cancer diagnosis has been widely reported, further studies are still required to address this challenging issue. The present study examined the expression profiles of EV-packaged miRNAs to identify novel miRNA signatures in breast cancer and verified their diagnostic accuracy. Circulating EVs were isolated from healthy controls and breast cancer patients and characterized following the MISEV 2018 guidelines. RNA-sequencing and real-time PCR showed that miRNA-27a and miRNA-128 were significantly down-regulated in patient-derived EVs compared to controls in screening and validation cohorts. Bioinformatics analyses of miRNA-target genes indicated several enriched biological processes/pathways related to breast cancer. Receiver operating characteristic (ROC) curves highlighted the ability of these EV-miRNAs to distinguish breast cancer patients from non-cancer controls. According to other reports, the levels of EV-miRNA-27a and EV-miRNA-128 are not associated with their circulating ones. Finally, evidence from the studies included in our systematic review underscores how the expression of these miRNAs in biofluids is still underinvestigated. Our findings unraveled the role of serum EV-derived miRNA-27a and miRNA-128 in breast cancer, encouraging further investigation of these two miRNAs within EVs towards improved breast cancer detection.
Topics: Humans; Female; MicroRNAs; Breast Neoplasms; Extracellular Vesicles
PubMed: 37958677
DOI: 10.3390/ijms242115695 -
International Journal of Molecular... Jun 2020The purpose of this review was to evaluate the expression patterns of miRNAs in periodontal and peri-implant diseases, while identifying potential miRNAs with the... (Meta-Analysis)
Meta-Analysis Review
AIM
The purpose of this review was to evaluate the expression patterns of miRNAs in periodontal and peri-implant diseases, while identifying potential miRNAs with the greatest diagnostic ability as an oral fluid biomarker.
MATERIALS AND METHODS
Human and animal studies were included when evaluating expression of miRNAs between health and different forms/stages of diseases, in which microarray and/or real-time polymerase chain reaction (RT-PCR) was carried out to detect fold changes in gene expression. After full-text analysis, 43 articles were considered for a qualitative assessment, and 16 miRNAs were selected to perform meta-analysis.
RESULTS
Based on human studies, results showed an overall upregulation of most of the evaluated miRNAs in periodontitis, with miRNA-142-3p and miRNA-146a being the most conclusive on both microarray and RT-PCR values and potentially serving as diagnostic biomarkers for disease activity. Conversely, miR-155 was the only miRNA revealing a statistically significant difference (SSD) ( < 0.05*) in experimental periodontitis models from RT-PCR values. Scarce scientific evidence is available from peri-implant diseases, however, most explored miRNAs in peri-implantitis were downregulated except for miR-145.
CONCLUSIONS
Although our results revealed that a distinct differential expression of specific miRNAs can be noted between the state of health and disease, future research remains necessary to explore the functional role of specific miRNAs and their potential as therapeutic targets in periodontal and peri-implant diseases. MeSH Terms: periodontitis, peri-implantitis, epigenomics, microarray analysis, real-time polymerase chain reaction, microRNAs.
CLINICAL RELEVANCE
Scientific background: Although most research identified different expression levels of miRNAs in periodontal and peri-implant diseases compared to their counterparts, their actual role in the pathogenesis of these conditions remains unclear. Therefore, we aimed to present a systematic review and meta-analysis on the expression patterns of miRNAs in periodontitis and peri-implantitis, while identifying potential miRNAs with the greatest diagnostic ability as an oral fluid biomarker.
PRINCIPAL FINDINGS
In periodontitis-related studies, miRNA-142-3p and miRNA-146a were the most conclusive on both microarray and RT-PCR values. Scarce scientific evidence is available from peri-implant diseases.
PRACTICAL IMPLICATIONS
Both miRNA-142-3p and miRNA-146a might serve as future diagnostic biomarkers for disease activity in periodontitis. Yet, future research remains necessary to explore the functional role of specific miRNAs and their potential as therapeutic targets in periodontal and peri-implant diseases.
Topics: Animals; Biomarkers; Humans; MicroRNAs; Oligonucleotide Array Sequence Analysis; Peri-Implantitis; Periodontitis
PubMed: 32532036
DOI: 10.3390/ijms21114147 -
Medicine Nov 2019Recent genetic association studies showed conflicting results on the relationship of miRNA single-nucleotide polymorphisms (SNPs) and congenital heart disease (CHD)... (Meta-Analysis)
Meta-Analysis
PURPOSE
Recent genetic association studies showed conflicting results on the relationship of miRNA single-nucleotide polymorphisms (SNPs) and congenital heart disease (CHD) risk. The purpose of the present systematic review was to collect the current available evidences to evaluate the association between miRNA polymorphisms and CHD risk.
METHODS
Four electronic databases including PubMed, EMBASE, ISI Web of Science, and CENTRAL were extensively searched for relevant studies published before February, 2019. Observational studies determining the association between miRNA polymorphisms and risk of CHD were included. Risk of bias was evaluated using the Newcastle-Ottawa Scale by 2 independent researchers. Major characteristics of each study and estimation of effect size of individual locus polymorphism were summarized. In addition, meta-analysis was performed to quantify the associations between miRNA polymorphisms and CHD risk.
RESULTS
Nine studies containing 6502 CHD patients and 6969 healthy controls were included in this systematic review. Ten loci in 9 miRNAs were reported. Only rs11614913 in miR-196a2 was determined to have significant associations with CHD susceptibility, which was supported by meta-analysis (CC vs CT+TT: odds ratio 1.54, 95% confidence interval 1.30, 1.82; P < .00001). A strong evidence indicated lack of association between rs2910164 in miR-146a and CHD. Limited or conflicting evidences were found for the associations of the other variants (rs11134527, rs139365823, rs76987351, rs3746444, rs4938723, rs2292832, rs41291957, rs895819) and risk of CHD.
CONCLUSIONS
Locus polymorphisms in miRNAs are not generally associated with CHD. Only rs11614913 was found to have significant associations with CHD. Further studies will be needed, using larger populations of different ethnicities, to obtain a better understanding of these associations.
Topics: Genetic Association Studies; Genetic Predisposition to Disease; Heart Defects, Congenital; Humans; MicroRNAs; Odds Ratio; Polymorphism, Single Nucleotide
PubMed: 31702616
DOI: 10.1097/MD.0000000000017653 -
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 -
Journal of Oral Pathology & Medicine :... Apr 2021miRNA is one of the advanced epigenetic molecular markers correlating with lymph node metastasis in patients with Oral squamous cell carcinoma (OSCC). Numerous published... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
miRNA is one of the advanced epigenetic molecular markers correlating with lymph node metastasis in patients with Oral squamous cell carcinoma (OSCC). Numerous published papers are showing correlation of miRNA with metastasis. There is a need to analyze and validate such correlation.
METHOD
English language literature in major databases from the last 20 years was searched using controlled vocabulary and keywords. Strict inclusion and exclusion criteria were followed for selection of studies. The quality assessment was done as per the QUADAS tool 2 by three independent reviewers. The metanalysis was performed by using random effect model. Standardized mean difference (SMD) was considered as the effect measure. Statistical software used was STATA version 13.1.
RESULTS
With all inclusion and exclusion criteria, eight studies could qualify for metanalysis. The pooled estimate is found to be 0.13 (-0.35, 0.62), P = .585, which is statistically not significant. This indicates that there is a no significant difference in the fold change between metastasis and no metastasis groups. P-value of chi-square statistic for heterogeneity is <.001 (significant), and I-squared statistic is 87.2%, which indicates that heterogeneity is present to a considerable extent. Egger's test shows there is no publication bias involved (P = .819).
CONCLUSION
The metanalysis showed no significant difference in the fold change of miRNA expression between metastasis and non-metastasis OSCC patients. Future studies can be directed to eliminate the heterogeneity among the studies noted in this analysis to confirm the role of miRNA for assessment of regional metastasis with special focus on tongue squamous cell carcinoma.
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Lymph Nodes; Lymphatic Metastasis; MicroRNAs; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck; Tongue Neoplasms
PubMed: 33220092
DOI: 10.1111/jop.13134 -
Journal of Translational Medicine Jan 2021The ability of tumor cells to spread from their origin place and form secondary tumor foci is determined by the epithelial-mesenchymal transition process. In epithelial... (Meta-Analysis)
Meta-Analysis Review
The ability of tumor cells to spread from their origin place and form secondary tumor foci is determined by the epithelial-mesenchymal transition process. In epithelial tumors such as prostate cancer (PCa), the loss of intercellular interactions can be observed as a change in expression of polarity proteins. Epithelial cells acquire ability to migrate, what leads to the formation of distal metastases. In recent years, the interest in miRNA molecules as potential future treatment options has increased. In tumor microenvironment, miRNAs have the ability to regulate signal transduction pathways, where they can act as suppressors or oncogenes. MiRNAs are secreted by cancer cells, and the changes in their expression levels are closely related to a cancer progression, including epithelial-mesenchymal transition. These molecules offer new diagnostic and therapeutic possibilities. Therapeutics which make use of synthesized RNA fragments and mimic or block miRNAs affected in PCa, may lead to inhibition of tumor progression and even disease re-emission. Based on appropriate qualification criteria, we conducted a selection process to identify scientific articles describing miRNAs and their relation to epithelial-mesenchymal transition in PCa patients. The studies were published in English on Pubmed, Scopus and the Web of Science before August 08, 2019. Hazard ratios (HRs) and 95% confidence intervals (CI) as well as total Gleason score were used to assess the concordance between miRNAs and presence of metastases. A total of 13 studies were included in our meta-analysis, representing 1608 PCa patients and 15 miRNA molecules. Our study clarifies a relationship between the clinicopathological features of PCa and the aberrant expression of several miRNA as well as the complex mechanism of miRNA molecules involvement in the induction and promotion of the metastatic mechanism in PCa.
Topics: Cell Line, Tumor; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Humans; Male; MicroRNAs; Neoplasm Grading; Prognosis; Prostatic Neoplasms; Tumor Microenvironment
PubMed: 33413466
DOI: 10.1186/s12967-020-02644-x -
Free Radical Biology & Medicine Aug 2021Although myocardial ischemia-reperfusion injury (I/R) and its pathological consequences are the leading cause of morbidity and mortality worldwide, cardioprotective... (Review)
Review
Systematic review and network analysis of microRNAs involved in cardioprotection against myocardial ischemia/reperfusion injury and infarction: Involvement of redox signalling.
Although myocardial ischemia-reperfusion injury (I/R) and its pathological consequences are the leading cause of morbidity and mortality worldwide, cardioprotective therapeutics are still not on the market. Oxidative stress, a major contributing factor to myocardial I/R, changes transcription of coding and non-coding RNAs, alters post-transcriptional modulations, and regulate protein function. MicroRNA (miRNA) expression can be altered by oxidative stress and microRNAs may also regulate cytoprotective mechanisms and exert cardioprotection againts I/R. Transcriptomic analysis of I/R and oxidative stress-induced alterations followed by microRNA-mRNA target interaction network analysis may reveal microRNAs and their mRNA targets that may play a role in cardioprotection and serve as microRNA therapeutics or novel molecular targets for further drug development. Here we provide a summary of a systematic literature review and in silico molecular network analysis to reveal important cardioprotective microRNAs and their molecular targets that may provide cardioprotection via regulation of redox signalling.
Topics: Humans; Infarction; MicroRNAs; Myocardial Reperfusion Injury; Oxidation-Reduction; Signal Transduction
PubMed: 33965565
DOI: 10.1016/j.freeradbiomed.2021.04.034 -
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 -
Cells Jul 2023Osteoarthritis (OA) is a joint disorder characterized by progressive degeneration of cartilage extracellular matrix (ECM), chondrocyte hypertrophy and apoptosis and... (Review)
Review
Epigenetic Modifications of MiRNAs in Osteoarthritis: A Systematic Review on Their Methylation Levels and Effects on Chondrocytes, Extracellular Matrix and Joint Inflammation.
Osteoarthritis (OA) is a joint disorder characterized by progressive degeneration of cartilage extracellular matrix (ECM), chondrocyte hypertrophy and apoptosis and inflammation. The current treatments mainly concern pain control and reduction of inflammation, but no therapeutic strategy has been identified as a disease-modifying treatment. Therefore, identifying specific biomarkers useful to prevent, treat or distinguish the stages of OA disease has become an immediate need of clinical practice. The role of microRNAs (miRNAs) in OA has been investigated in the last decade, and increasing evidence has emerged that the influence of the environment on gene expression through epigenetic processes contributes to the development, progression and aggressiveness of OA, in particular acting on the microenvironment modulations. The effects of epigenetic regulation, particularly different miRNA methylation during OA disease, were highlighted in the present systematic review. The evidence arising from this study of the literature conducted in three databases (PubMed, Scopus, Web of Science) suggested that miRNA methylation state already strongly impacts OA progression, driving chondrocytes and synoviocyte proliferation, apoptosis, inflammation and ECM deposition. However, the possibility of understanding the mechanism by which different epigenetic modifications of miRNA or pre-miRNA sequences drive the aggressiveness of OA could be the new focus of future investigations.
Topics: Humans; Chondrocytes; MicroRNAs; Epigenesis, Genetic; Methylation; Osteoarthritis; Inflammation; Extracellular Matrix
PubMed: 37508486
DOI: 10.3390/cells12141821