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Oncotarget Sep 2016Asbestos is a harmful and exceptionally persistent natural material. Malignant mesothelioma (MM), an asbestos-related disease, is an insidious, lethal cancer that is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Asbestos is a harmful and exceptionally persistent natural material. Malignant mesothelioma (MM), an asbestos-related disease, is an insidious, lethal cancer that is poorly responsive to current treatments. Minimally invasive, specific, and sensitive biomarkers providing early and effective diagnosis in high-risk patients are urgently needed. MicroRNAs (miRNAs, miRs) are endogenous, non-coding, small RNAs with established diagnostic value in cancer and pollution exposure. A systematic review and a qualitative meta-analysis were conducted to identify high-confidence miRNAs that can serve as biomarkers of asbestos exposure and MM.
METHODS
The major biomedical databases were systematically searched for miRNA expression signatures related to asbestos exposure and MM. The qualitative meta-analysis applied a novel vote-counting method that takes into account multiple parameters. The most significant miRNAs thus identified were then subjected to functional and bioinformatic analysis to assess their biomarker potential.
RESULTS
A pool of deregulated circulating and tissue miRNAs with biomarker potential for MM was identified and designated as "mesomiRs" (MM-associated miRNAs). Comparison of data from asbestos-exposed and MM subjects found that the most promising candidates for a multimarker signature were circulating miR-126-3p, miR-103a-3p, and miR-625-3p in combination with mesothelin. The most consistently described tissue miRNAs, miR-16-5p, miR-126-3p, miR-143-3p, miR-145-5p, miR-192-5p, miR-193a-3p, miR-200b-3p, miR-203a-3p, and miR-652-3p, were also found to provide a diagnostic signature and should be further investigated as possible therapeutic targets.
CONCLUSION
The qualitative meta-analysis and functional investigation confirmed the early diagnostic value of two miRNA signatures for MM. Large-scale, standardized validation studies are needed to assess their clinical relevance, so as to move from the workbench to the clinic.
Topics: Asbestos; Biomarkers, Tumor; Computational Biology; Epigenesis, Genetic; GPI-Linked Proteins; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Mesothelin; Mesothelioma; Mesothelioma, Malignant; MicroRNAs; Oligonucleotide Array Sequence Analysis; Phenotype; Tissue Array Analysis; Tissue Distribution
PubMed: 27259231
DOI: 10.18632/oncotarget.9686 -
The Plant Journal : For Cell and... Mar 2023High yield and stress resistance are the major prerequisites for successful crop cultivation, and can be achieved by modifying plant architecture. Evolutionarily... (Review)
Review
High yield and stress resistance are the major prerequisites for successful crop cultivation, and can be achieved by modifying plant architecture. Evolutionarily conserved growth-regulating factors (GRFs) control the growth of different tissues and organs of plants. Here, we provide a systematic overview of the expression patterns of GRF genes and the structural features of GRF proteins in different plant species. Moreover, we illustrate the conserved and divergent roles of GRFs, microRNA396 (miR396), and GRF-interacting factors (GIFs) in leaf, root, and flower development. We also describe the molecular networks involving the miR396-GRF-GIF module, and illustrate how this module coordinates with different signaling molecules and transcriptional regulators to control development of different plant species. GRFs promote leaf growth, accelerate grain filling, and increase grain size and weight. We also provide some molecular insight into how coordination between GRFs and other signaling modules enhances crop productivity; for instance, how the GRF-DELLA interaction confers yield-enhancing dwarfism while increasing grain yield. Finally, we discuss how the GRF-GIF chimera substantially improves plant transformation efficiency by accelerating shoot formation. Overall, we systematically review the conserved and divergent roles of GRFs and the miR396-GRF-GIF module in growth regulation, and also provide insights into how GRFs can be utilized to improve the productivity and nutrient content of crop plants.
Topics: Plants, Genetically Modified; Gene Expression Regulation, Plant; MicroRNAs; Plant Development; Plant Leaves; Intercellular Signaling Peptides and Proteins
PubMed: 36582168
DOI: 10.1111/tpj.16090 -
Cell Death & Disease Apr 2024N6-methyladenosine (m6A) methylation, a prevalent eukaryotic post-transcriptional modification, is involved in multiple biological functions, including mediating... (Review)
Review
N6-methyladenosine (m6A) methylation, a prevalent eukaryotic post-transcriptional modification, is involved in multiple biological functions, including mediating variable splicing, RNA maturation, transcription, and nuclear export, and also is vital for regulating RNA translation, stability, and cytoplasmic degradation. For example, m6A methylation can regulate pre-miRNA expression by affecting both splicing and maturation. Non-coding RNA (ncRNA), which includes microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), does not encode proteins but has powerful impacts on transcription and translation. Conversely, ncRNAs may impact m6A methylation by affecting the expression of m6A regulators, including miRNAs targeting mRNA of m6A regulators, or lncRNAs, and circRNAs, acting as scaffolds to regulate transcription of m6A regulatory factors. Dysregulation of m6A methylation is common in urinary tumors, and the regulatory role of ncRNAs is also important for these malignancies. This article provides a systematic review of the role and mechanisms of action of m6A methylation and ncRNAs in urinary tumors.
Topics: Humans; RNA, Long Noncoding; RNA, Circular; RNA, Untranslated; Neoplasms; MicroRNAs; Adenosine
PubMed: 38632251
DOI: 10.1038/s41419-024-06664-z -
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 -
Oncotarget Oct 2016Recent studies revealed that different microRNA-9 (miR-9) expressions were associated with prognoses of different cancers. We conducted this meta-analysis to evaluate... (Meta-Analysis)
Meta-Analysis Review
Recent studies revealed that different microRNA-9 (miR-9) expressions were associated with prognoses of different cancers. We conducted this meta-analysis to evaluate the prognostic value of miR-9. PubMed, Embase, Web of Science, and Cochrane Library (last update by November 30, 2015) were searched for literatures. A total of 17 studies from 16 articles were finally qualified and enrolled in this meta-analysis. Pooled analyses showed that a higher expression of miR-9 might predict poor overall survival (HR: 2.17, 95% CI: 1.39 - 3.41, P < 0.001 (7.23 * 10-4)), disease-free survival (HR: 5.22, 95% CI: 2.17 - 12.53, P < 0.001 (2.21 * 10-4)), and recurrence-free survival (HR: 1.57, 95% CI: 1.32 - 1.85, P < 0.001 (1.80*10-7)) in various carcinomas. However, results of subgroup analyses revealed that down-regulated miR-9 was associated with poor overall survival (HR: 0.45, 95% CI: 0.28 - 0.73, P < 0.001 (1.13*10-3)) and progress-free survival (HR: 0.46, 95% CI: 0.34 - 0.62, P < 0.001 (5.03*10-7)) in ovarian cancer patients. By subgroup analyses we also found that sample collecting time and patients' origin had little influence on the result of OS. These results indicate that in most cancer types the highly expressed miR-9 is associated with poor survival of patients, whereas the down-regulated miR-9 may predict poor prognosis in patients with ovarian cancer.
Topics: Biomarkers, Tumor; Humans; MicroRNAs; Neoplasms; Prognosis
PubMed: 27563807
DOI: 10.18632/oncotarget.11466 -
Cellular Physiology and Biochemistry :... 2015Recently, many studies have shown that microRNAs (miRNA) exhibit altered expression in various cancers and may serve as prognostic biomarkers. We performed a systematic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recently, many studies have shown that microRNAs (miRNA) exhibit altered expression in various cancers and may serve as prognostic biomarkers. We performed a systematic review and meta-analysis to evaluate the prognostic role of miR-200c expression in different cancers.
METHODS
Studies were recruited by searching PubMed, Embase and the Cochrane Library (last search update was May 2014) and assessed by further quality evaluation.
RESULTS
A total of 25 studies dealing with various carcinomas were identified for systematic review. Among them, 18 studies were ultimately included in the meta-analysis. Our results indicated that the expression of tissue miR-200c was not associated with OS and PFS in various carcinomas; however, downregulation of tissue miR-200c did predict poor OS of patients with stage I disease (HR=0.41, 95% CI 0.25-0.68, P=0.001). Furthermore, overexpression of blood miR-200c was significantly related to poor OS and PFS (HR=3.07 95% CI 1.58-5.96 P=0.001, HR=2.26 95% CI 1.66-3.08 P<0.001, respectively), especially in patients with advanced disease.
CONCLUSION
This systematic review and meta-analysis clarified that low expression of miR-200c in primary tissue was significantly associated with poor survival in cancer patients at early stage, whereas a high level of blood miR-200c predicted poor prognosis in patients with advanced tumors.
Topics: Biomarkers, Tumor; Humans; MicroRNAs; Neoplasm Staging; Neoplasms; Neoplastic Cells, Circulating; Prognosis; Survival Analysis
PubMed: 25766530
DOI: 10.1159/000373943 -
BioMed Research International 2021It has been shown that miR-192 is abnormally expressed in a variety of cancer types and participates in different kinds of signaling pathways. The role of miR-192 in the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
It has been shown that miR-192 is abnormally expressed in a variety of cancer types and participates in different kinds of signaling pathways. The role of miR-192 in the diagnosis and prognosis of cancer has not been verified. This article is aimed at exploring the diagnostic and prognostic value of miR-192 through a systematic review and meta-analysis.
METHODS
A systematic search was performed through PubMed, Embase, Web of Science, and Cochrane Library databases up to June 16, 2020. A total of 16 studies were enrolled in the meta-analyses, of which 11 articles were used for diagnostic meta-analysis and 5 articles were used for prognostic meta-analysis. The values of sensitivity and specificity using miR-192 expression as a diagnostic tool were pooled in the diagnostic meta-analysis. The hazard ratios (HRs) of overall survival (OS) with 95 confidence intervals (CIs) were extracted from the studies, and pooled HRs were evaluated in the prognostic meta-analysis. Eleven studies including 667 cancer patients and 514 controls met the eligibility criteria for the diagnostic meta-analysis. Five studies including 166 patients with high miR-192 expression and 236 patients with low miR-192 expression met the eligibility criteria for the prognostic meta-analysis.
RESULTS
The overall diagnostic accuracy was as follows: sensitivity 0.79 (95%CI = 0.75-0.82), specificity 0.74 (95%CI = 0.64-0.82), positive likelihood ratio 3.03 (95%CI = 2.11-4.34), negative likelihood ratio 0.29 (95%CI = 0.23-0.37), diagnostic odds ratio 10.50 (95%CI = 5.89-18.73), and area under the curve ratio (AUC) 0.82 (95%CI = 0.78-0.85). The overall prognostic analysis showed that high expression of miR-192 in patients was associated with positive survival (HR = 0.62, 95%CI : 0.41-0.93, = 0.020).
CONCLUSION
Our results revealed that miR-192 was a potential biomarker with good sensitivity and specificity in cancers. Moreover, highly expressed miR-192 predicted a good prognosis for patients.
Topics: Biomarkers, Tumor; Female; Humans; Male; MicroRNAs; Neoplasms; Prognosis; Sensitivity and Specificity
PubMed: 33614788
DOI: 10.1155/2021/8851035 -
Oncotarget Jul 2017Gastrointestinal cancers (GICs) mainly including esophageal, gastric and colorectal cancer, are the most common cause of cancer-related death and lead into high... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gastrointestinal cancers (GICs) mainly including esophageal, gastric and colorectal cancer, are the most common cause of cancer-related death and lead into high mortality worldwide. We performed this systematic review and meta-analysis to elucidate relationship between multiple microRNAs (miRs) expression and survival of GIC patients.
METHODS
We searched a wide range of database. Fixed-effects and random-effects models were used to calculate the pooled hazard ratio values of overall survival and disease free survival. In addition, funnel plots were used to qualitatively analyze the publication bias and verified by Begg's test while it seems asymmetry.
RESULTS
60 studies involving a total of 6225 patients (1271 with esophageal cancer, 3467 with gastric cancer and 1517 with colorectal cancer) were included in our meta-analysis. The pooled hazard ratio values of overall survival related to different miRs expression in esophageal, gastric, colorectal and gastrointestinal cancer were 2.10 (1.78-2.49), 2.02 (1.83-2.23), 2.54 (2.14-3.02) and 2.15 (1.99-2.31), respectively. We have identified a total of 59 miRs including 23 significantly up-regulated expression miRs (miR-214, miR-17, miR-20a, miR-200c, miR-107, miR-27a, etc.) and 36 significantly down-regulated expression miRs (miR-433, let-7g, miR-125a-5p, miR-760, miR-206, miR-26a, miR-200b, miR-185, etc.) correlated with poor prognosis in GIC patients. Moreover, 35 of them revealed mechanisms.
CONCLUSION
Overall, specific miRs are significantly associated with the prognosis of GIC patients and potentially eligible for the prediction of patients survival. It also provides a potential value for clinical decision-making development and may serve as a promising miR-based target therapy waiting for further elucidation.
Topics: Biomarkers, Tumor; Gastrointestinal Neoplasms; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; MicroRNAs; Prognosis; Proportional Hazards Models; RNA Interference; RNA, Messenger
PubMed: 28402940
DOI: 10.18632/oncotarget.16679 -
International Journal of Molecular... Aug 2022Sepsis is a critical condition characterized by increased levels of pro-inflammatory cytokines and proliferating cells such as neutrophils and macrophages in response to... (Review)
Review
Sepsis is a critical condition characterized by increased levels of pro-inflammatory cytokines and proliferating cells such as neutrophils and macrophages in response to microbial pathogens. Such processes lead to an abnormal inflammatory response and multi-organ failure. MicroRNAs (miRNA) are single-stranded non-coding RNAs with the function of gene regulation. This means that miRNAs are involved in multiple intracellular pathways and thus contribute to or inhibit inflammation. As a result, their variable expression in different tissues and organs may play a key role in regulating the pathophysiological events of sepsis. Thanks to this property, miRNAs may serve as potential diagnostic and prognostic biomarkers in such life-threatening events. In this narrative review, we collect the results of recent studies on the expression of miRNAs in heart, blood, lung, liver, brain, and kidney during sepsis and the molecular processes in which they are involved. In reviewing the literature, we find at least 122 miRNAs and signaling pathways involved in sepsis-related organ dysfunction. This may help clinicians to detect, prevent, and treat sepsis-related organ failures early, although further studies are needed to deepen the knowledge of their potential contribution.
Topics: Gene Expression Regulation; Humans; Macrophages; MicroRNAs; Multiple Organ Failure; Sepsis
PubMed: 36012630
DOI: 10.3390/ijms23169354 -
Experimental and Therapeutic Medicine Aug 2022Single nucleotide polymorphism (SNP) of long noncoding RNA (lnc)RNA has been reported to be an important factor in cancer development. Recently, lncRNA homeobox...
Single nucleotide polymorphism (SNP) of long noncoding RNA (lnc)RNA has been reported to be an important factor in cancer development. Recently, lncRNA homeobox transcript antisense intergenic RNA (HOTAIR) was indicated to induce tumorigenesis of several cancer types, but the association between the SNP of lncRNA HOTAIR and lung cancer susceptibility has remained undetermined. The present meta-analysis aimed to investigate the effect of HOTAIR polymorphism on susceptibility to lung cancer. The PubMed, Ovid Medline, Embase and Cochrane Library databases were thoroughly searched. Studies containing data on the incidence of lung cancer in patients with different HOTAIR SNPs were included. The Hardy-Weinberg equilibrium was analyzed to determine genotype distribution and allele frequencies. The odds ratio (OR) was pooled to evaluate the association of different SNPs with the susceptibility to lung cancer. A total of six studies comprising 1,715 patients with lung cancer and 2,745 healthy controls were finally included. A total of 4 SNPs (rs12826786, rs1899663, rs920778 and rs4759314) were reported. Analyses for all of these SNPs individually indicated that the lncRNA HOTAIR rs1899663 C>A polymorphism was a risk factor for lung cancer (dominant mode, AA+CA vs. CC: OR=0.816, 95% CI=0.707-0.942, P=0.005). The present study was the first meta-analysis investigating the association between lncRNA HOTAIR and lung cancer susceptibility. The results indicated that the lncRNA HOTAIR rs1899663 C>A polymorphism is a risk factor for lung cancer. LncRNA HOTAIR may be of value in lung cancer screening, particularly for populations with high-risk factors, as well as prognosis prediction. Future investigations are required to further clarify the intrinsic mechanism of the role of HOTAIR in the oncogenesis of lung cancer.
PubMed: 35837044
DOI: 10.3892/etm.2022.11477