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Molecular Neurobiology Sep 2019Currently there are 850,000 people with Alzheimer's disease in the UK, with an estimated rise to 1.1 million by 2025. Alzheimer's disease is characterised by the...
Currently there are 850,000 people with Alzheimer's disease in the UK, with an estimated rise to 1.1 million by 2025. Alzheimer's disease is characterised by the accumulation of amyloid-beta plaques and hyperphosphorylated tau in the brain causing a progressive decline in cognitive impairment. Small non-coding microRNA (miRNA) sequences have been found to be deregulated in the peripheral blood of Alzheimer patients. A systematic review was conducted to extract all miRNA found to be significantly deregulated in the peripheral blood. These deregulated miRNAs were cross-referenced against the miRNAs deregulated in the brain at Braak Stage III. This resulted in a panel of 10 miRNAs (hsa-mir-107, hsa-mir-26b, hsa-mir-30e, hsa-mir-34a, hsa-mir-485, hsa-mir200c, hsa-mir-210, hsa-mir-146a, hsa-mir-34c, and hsa-mir-125b) hypothesised to be deregulated early in Alzheimer's disease, nearly 20 years before the onset of clinical symptoms. After network analysis of the 10 miRNAs, they were found to be associated with the immune system, cell cycle, gene expression, cellular response to stress, neuron growth factor signalling, wnt signalling, cellular senescence, and Rho GTPases.
Topics: Alzheimer Disease; Animals; Biomarkers; Brain; Gene Regulatory Networks; Humans; MicroRNAs
PubMed: 30734227
DOI: 10.1007/s12035-019-1500-y -
Progress in Neurobiology Nov 2019While the root causes for individual neurodegenerative diseases are distinct, many shared pathological features and mechanisms contribute to neurodegeneration across...
While the root causes for individual neurodegenerative diseases are distinct, many shared pathological features and mechanisms contribute to neurodegeneration across diseases. Altered levels of microRNAs, small non-coding RNAs involved in post transcriptional regulation of gene expression, are reported for numerous neurodegenerative diseases. Yet, comparison between diseases to uncover commonly dysregulated microRNAs during neurodegeneration in general is lagging. We performed a systematic review of peer-reviewed publications describing differential microRNA expression in neurodegenerative diseases and related animal models. We compiled the results from studies covering the prevalent neurodegenerative diseases in the literature: Alzheimer's disease, amyotrophic lateral sclerosis, age-related macular degeneration, ataxia, dementia, myotonic dystrophy, epilepsy, glaucoma, Huntington's disease, multiple sclerosis, Parkinson's disease, and prion disorders. MicroRNAs which were dysregulated most often in these diseases and their models included miR-9-5p, miR-21-5p, the miR-29 family, miR-132-3p, miR-124-3p, miR-146a-5p, miR-155-5p, and miR-223-3p. Common pathways targeted by these predominant miRNAs were identified and revealed great functional overlap across diseases. We also identified a strong role for each microRNA in both the neural and immune components of diseases. microRNAs regulate broad networks of genes and identifying microRNAs commonly dysregulated across neurodegenerative diseases could cultivate novel hypotheses related to common molecular mechanisms underlying neurodegeneration.
Topics: Animals; Brain; Disease Models, Animal; Gene Expression Regulation; Humans; MicroRNAs; Neurodegenerative Diseases
PubMed: 31356849
DOI: 10.1016/j.pneurobio.2019.101664 -
International Journal of Molecular... Jan 2019Recently extensive focus has been concentrated on the role of miRNAs in the initiation and progression of cardio-cerebrovascular diseases (CCDs) which constitute a range... (Meta-Analysis)
Meta-Analysis
Recently extensive focus has been concentrated on the role of miRNAs in the initiation and progression of cardio-cerebrovascular diseases (CCDs) which constitute a range of conditions including cardiovascular diseases (CVDs, especially coronary artery disease (CAD)), congenital heart disease (CHD) and cerebrovascular diseases (CBVDs, especially the ischemic stroke (IS)). An increasing number of studies are evaluating the association between different miRNA polymorphisms and risk of CCDs, but results have been inconclusive. This study represents a comprehensive systematic review and meta-analysis of the association between miRNA polymorphisms and risk of CCDs. PubMed, Embase, Scopus, and Web of Science were queried to identify eligible articles. Odds ratios and 95% confidence intervals were used to assess the association of miRNA polymorphisms with CCD susceptibility. A total of 51 eligible articles evaluating the association of 31 miRNA polymorphisms were identified. Meta-analysis was performed for six miRNA polymorphisms. miR-146a rs2910164 (30 studies: 13,186 cases/14,497 controls), miR-149 rs2292832 (Nine studies: 4116 cases/3511 controls), miR-149 rs71428439 (Three studies: 1556 cases/1567 controls), miR-196a2 rs11614913 (20 studies: 10,144 cases/10,433 controls), miR-218 rs11134527 (Three studies: 2,322 cases/2,754 controls) were not associated with overall CCD. miR-499 rs3746444 was associated with CCD (20 studies: 9564 cases/8876 controls). In the subgroups, rs2910164 and rs3746444 were only associated with CVDs, especially CAD. In conclusion, the results support the existence of a role for miR-146a rs2910164 and miR-499 rs3746444 in determining susceptibility to CCDs, especially CAD.
Topics: Cardiovascular Diseases; Cerebrovascular Disorders; Coronary Artery Disease; Genetic Association Studies; Genetic Predisposition to Disease; Humans; MicroRNAs; Odds Ratio; Polymorphism, Single Nucleotide
PubMed: 30642078
DOI: 10.3390/ijms20020293 -
Frontiers in Immunology 2023Sjögren's syndrome (SS) is a systemic autoimmune disease, which affects the exocrine glands leading to glandular dysfunction and, particularly, symptoms of oral and...
INTRODUCTION
Sjögren's syndrome (SS) is a systemic autoimmune disease, which affects the exocrine glands leading to glandular dysfunction and, particularly, symptoms of oral and ocular dryness. The aetiology of SS remains unclear, and the disease lacks distinctive clinical features. The current diagnostic work-up is complex, invasive and often time-consuming. Thus, there is an emerging need for identifying disease-specific and, ideally, non-invasive immunological and molecular biomarkers that can simplify the diagnostic process, allow stratification of patients, and assist in monitoring the disease course and outcome of therapeutic intervention in SS.
METHODS
This systematic review addresses the use of proteomics and miRNA-expression profile analyses in this regard.
RESULTS AND DISCUSSION
Out of 272 papers that were identified and 108 reviewed, a total of 42 papers on proteomics and 23 papers on miRNA analyses in saliva, blood and salivary gland tissue were included in this review. Overall, the proteomic and miRNA studies revealed considerable variations with regard to candidate biomarker proteins and miRNAs, most likely due to variation in sample size, processing and analytical methods, but also reflecting the complexity of SS and patient heterogeneity. However, interesting novel knowledge has emerged and further validation is needed to confirm their potential role as biomarkers in SS.
Topics: Humans; Sjogren's Syndrome; MicroRNAs; Proteomics; Saliva; Biomarkers
PubMed: 37275849
DOI: 10.3389/fimmu.2023.1183195 -
Biomarkers in Medicine Feb 2022There are a plethora of publications on the role of miRNA gene polymorphism and its association with recurrent pregnancy loss (RPL), but a lack of uniformity in the... (Meta-Analysis)
Meta-Analysis Review
There are a plethora of publications on the role of miRNA gene polymorphism and its association with recurrent pregnancy loss (RPL), but a lack of uniformity in the studies available due to the variable subject population, heterogeneity and contrary results of significance. Rigorous data mining was done through PubMed, SCOPUS, Cochrane library, Elsevier and Google Scholar to extract the studies of interest published until June 2021. A total of eight SNPs of miRNAs have been included, where ≥2 studies per SNPs were available. Analysis was done on the basis of pooled odds ratios and 95% CI. This is the first meta-analysis on miRNA SNPs in RPL that suggests that rs11614913, rs3746444 and rs2292832 biomarkers may decrease the risk of RPL under different genetic models.
Topics: Abortion, Habitual; Female; Genetic Predisposition to Disease; Humans; MicroRNAs; Odds Ratio; Polymorphism, Single Nucleotide; Pregnancy
PubMed: 35026953
DOI: 10.2217/bmm-2021-0568 -
Cellular Physiology and Biochemistry :... 2015Aberrant microRNA expression has the potential to be used for early diagnosis of gastric cancer or to predict survival and treatment response. This study performed a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIMS
Aberrant microRNA expression has the potential to be used for early diagnosis of gastric cancer or to predict survival and treatment response. This study performed a systematic review and meta-analysis of altered miRNAs in gastric cancer in order to assess the use of miRNAs as novel biomarkers for early detection and prognosis prediction of gastric cancer.
METHODS
We retrieved published articles from the PubMed online database and obtained different sets of data on miRNAs expression profiling in gastric cancer and highlighted the most frequently dysregulated miRNAs in gastric cancer. We then extracted studies that used quantitative RT-PCR and then pooled them together by using meta-disc software (version 1.4).
RESULTS
We found that there were 47 aberrantly expressed miRNAs in gastric cancer (29 up-regulated and 18 down-regulated) that were most frequently reported in the literature. In publications that provided information on specific miRNA expression vs. diagnostic value, the pooled data showed good sensitivity and specificity as well as high levels of overall accuracy. However, specimen types could be a factor that introduces substantial heterogeneity. Published studies also showed association of altered miRNA expression with clinicopathological data from gastric cancer patients.
CONCLUSION
Thus, various miRNAs are differentially expressed in gastric cancer and some of them could be further evaluated as biomarkers for early diagnosis of gastric cancer and prediction of prognosis or treatment response.
Topics: Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Oligonucleotide Array Sequence Analysis; Prognosis; Stomach Neoplasms
PubMed: 25633747
DOI: 10.1159/000369750 -
Differentially expressed genes in the pre-eclamptic placenta: a systematic review and meta-analysis.PloS One 2013To systematically review the literature on human gene expression data of placental tissue in pre-eclampsia and to characterize a meta-signature of differentially... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically review the literature on human gene expression data of placental tissue in pre-eclampsia and to characterize a meta-signature of differentially expressed genes in order to identify novel putative diagnostic markers.
DATA SOURCES
Medline through 11 February 2011 using MeSH terms and keywords related to placenta, gene expression and gene expression arrays; GEO database using the term "placent*"; and reference lists of eligible primary studies, without constraints.
METHODS
From 1068 studies retrieved from the search, we included original publications that had performed gene expression array analyses of placental tissue in the third trimester and that reported on differentially expressed genes in pre-eclampsia versus normotensive controls. Two reviewers independently identified eligible studies, extracted descriptive and gene expression data and assessed study quality. Using a vote-counting method based on a comparative meta-profiling algorithm, we determined a meta-signature that characterizes the significant intersection of differentially expressed genes from the collection of independent gene signatures.
RESULTS
We identified 33 eligible gene expression array studies of placental tissue in the 3(rd) trimester comprising 30 datasets on mRNA expression and 4 datasets on microRNA expression. The pre-eclamptic placental meta-signature consisted of 40 annotated gene transcripts and 17 microRNAs. At least half of the mRNA transcripts encode a protein that is secreted from the cell and could potentially serve as a biomarker.
CONCLUSIONS
In addition to well-known and validated genes, we identified 14 transcripts not reported previously in relation to pre-eclampsia of which the majority is also expressed in the 1(st) trimester placenta, and three encode a secreted protein.
Topics: Female; Gene Expression Profiling; Gene Expression Regulation; Humans; MicroRNAs; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; RNA, Messenger; Signal Transduction
PubMed: 23874842
DOI: 10.1371/journal.pone.0068991 -
The Journal of Pain 2020Accumulating evidence suggests that epigenetic mechanisms may hold great potential in the field of pain. We systematically reviewed the literature exploring epigenetic...
Accumulating evidence suggests that epigenetic mechanisms may hold great potential in the field of pain. We systematically reviewed the literature exploring epigenetic mechanisms in people with pain. Four databases have been interrogated: MEDLINE, The Cochrane Central Register of Controlled Trial, Scopus, and Web of Science, following PRISMA guidelines in conducting study selection and assessment. Thirty-seven studies were included. Studies explored epigenetics in conditions such as fibromyalgia, CRPS, neuropathies, or osteoarthritis. Research focussed on genome-wide and gene-specific DNA methylation, and miRNA expression. Bioinformatics analyses exploring miRNA-associated molecular pathways were also performed. Several genes already known for their role in pain (BDNF, HDAC4, PRKG1, IL-17, TNFRSF13B, etc.), and several miRNAs linked to inflammatory regulation, nociceptive signalling and protein kinases functions have been found to differ significantly between people with chronic pain and healthy controls. Although the studies included were cross-sectional in nature, and no conclusion on causal links between epigenetic changes and pain could be drawn, we summarised the large amount of data available in literature on the topic, highlighting results that have been replicated by independent investigations. The field of pain epigenetics appears very exciting and has all the potential to lead to remarkable scientific advances. However, high-quality, well-powered, longitudinal studies are warranted. PERSPECTIVE: Though more high-quality research is needed, available research exploring epigenetic mechanisms or miRNAs in people with pain shows that genes regulating synaptic plasticity and excitability, protein kinases, and elements of the immune system might hold great potential in understanding the pathophysiology of different conditions.
Topics: DNA Methylation; Epigenesis, Genetic; Humans; MicroRNAs; Pain
PubMed: 31837447
DOI: 10.1016/j.jpain.2019.12.002 -
International Journal of Molecular... Dec 2023Substance addiction is a chronic and relapsing brain disorder characterized by compulsive seeking and continued substance use, despite adverse consequences. The high... (Review)
Review
Substance addiction is a chronic and relapsing brain disorder characterized by compulsive seeking and continued substance use, despite adverse consequences. The high prevalence and social burden of addiction are indisputable; however, the available intervention is insufficient. The modulation of gene expression and aberrant adaptation of neural networks are attributed to the changes in brain functions under repeated exposure to addictive substances. Considerable studies have demonstrated that miRNAs are strong modulators of post-transcriptional gene expression in substance addiction. The emerging role of microRNA (miRNA) provides new insights into many biological and pathological processes in the central nervous system: their variable expression in different regions of the brain and tissues may play a key role in regulating the pathophysiological events of addiction. This work provides an overview of the current literature on miRNAs involved in addiction, evaluating their impaired expression and regulatory role in neuroadaptation and synaptic plasticity. Clinical implications of such modulatory capacities will be estimated. Specifically, it will evaluate the potential diagnostic role of miRNAs in the various stages of drug and substance addiction. Future perspectives about miRNAs as potential novel therapeutic targets for substance addiction and abuse will also be provided.
Topics: Humans; MicroRNAs; Substance-Related Disorders; Behavior, Addictive; Brain
PubMed: 38069445
DOI: 10.3390/ijms242317122 -
Biomolecules Oct 2022Myocarditis and inflammatory dilated cardiomyopathy are cardiac diseases leading to heart failure. Liquid biopsy is a concept of replacing traditional biopsy with... (Review)
Review
Myocarditis and inflammatory dilated cardiomyopathy are cardiac diseases leading to heart failure. Liquid biopsy is a concept of replacing traditional biopsy with specialized blood tests. The study aim was to summarize and assess the usefulness of microRNAs and circulating free DNA as biomarkers of myocardial inflammation. For this systematic review, we searched Scopus, Embase, Web of Science, and PubMed. All studies measuring microRNAs in serum/plasma/cardiac tissue or circulating free DNA during myocarditis and non-ischemic dilated cardiomyopathy in humans in which healthy subjects or another cardiac disease served as a comparator were included. Data were extracted and miRNAs were screened and assessed using a scale created in-house. Then, highly graded miRNAs were assessed for usability as liquid biopsy biomarkers. Of 1185 records identified, 56 were eligible and 187 miRNAs were found. We did not identify any studies measuring circulating free DNA. In total, 24 of the screened miRNAs were included in the final assessment, 3 of which were selected as the best and 3 as potential candidates. We were not able to assess the risk of bias and the final inclusion decision was made by consensus. Serum levels of three miRNAs-miR-Chr8:96, miR-155, and miR-206-are the best candidates for myocardial inflammation liquid biopsy panel. Further studies are necessary to prove their role, specificity, and sensitivity.
Topics: Humans; Cardiomyopathy, Dilated; Myocarditis; MicroRNAs; Cell-Free Nucleic Acids; Biomarkers; Liquid Biopsy; Inflammation
PubMed: 36291684
DOI: 10.3390/biom12101476