-
Biomedical and Environmental Sciences :... Sep 2018Arsenic is a metalloid environmental carcinogen involved in the occurrence and development of many cancers. miRNA-21 plays a crucial role in arsenic-induced... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Arsenic is a metalloid environmental carcinogen involved in the occurrence and development of many cancers. miRNA-21 plays a crucial role in arsenic-induced carcinogenesis. We aimed to elucidate the mechanism by which miRNA-21 influences arsenic-induced cancer.
METHODS
We used meta-analysis of published studies to determine how arsenic induces cancerous cells through miRNA-21.
RESULTS
Low-dose arsenic exposure (⪕ 5 μmol/L) can increase miRNA-21 and phosphorylated signal transducter and activator of transcription 3 (pSTAT3) expression, and decrease programmed cell death protein 4 (PDCD4) and protein sprouty homolog 1 (Spry1) expression. High-dose arsenic exposure (> 5 μmol/L), can increase miRNA-21 expression, and decrease Spry1 and E-cadherin expression. Short-term arsenic exposure (⪕ 24 h) can increase miRNA-21 and pSTAT3 expression, and decrease PDCD4 expression. Moreover, long-term arsenic exposure (> 24 h) can increase the miRNA-21, STAT3, and pSTAT3 expression, and decrease PDCD4 expression. We found that activation of miRNA-21 and pSTAT3 were most pronounced following long-term arsenic exposure at low doses, and the effects on PDCD4 expression were most pronounced following short-term arsenic exposure at low doses. miRNA-21 inhibitors increased the expression of tumor suppressor genes PDCD4, PTEN, and Spry1 and miRNA-21-mimics suppressed the expression of these tumor suppressor genes.
CONCLUSION
Arsenic can cause cancer by activating miRNA-21 and inhibiting the expression of PDCD4, PTEN, and Spry1.
Topics: Apoptosis Regulatory Proteins; Arsenic; Gene Expression Regulation, Neoplastic; Humans; Membrane Proteins; MicroRNAs; Neoplasms; PTEN Phosphohydrolase; Phosphoproteins; RNA-Binding Proteins
PubMed: 30369344
DOI: 10.3967/bes2018.090 -
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 -
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 -
Medicine Nov 2023Lung cancer is the leading cause of death worldwide, and its diagnosis remains a significant challenge. Identifying effective methods to differentiate benign from... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lung cancer is the leading cause of death worldwide, and its diagnosis remains a significant challenge. Identifying effective methods to differentiate benign from malignant lung nodules is of paramount importance. This meta-analysis aimed to evaluate the clinical utility of circulating microRNAs (miRNAs) for the differential diagnosis of benign and malignant lung nodules.
METHODS
This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search was conducted across 4 electronic databases, without any temporal restrictions. The inclusion and exclusion criteria were strictly applied to assess the clinical applications of circulating miRNAs. A robust and transparent quality assessment was performed using the quality assessment of diagnostic accuracy studies-2 tool, and rigorous statistical analyses were conducted to synthesize the various diagnostic measures.
RESULTS
In the meta-analysis of 11 studies, quality assessment of diagnostic accuracy studies-2 assessment revealed < 5% high-risk methodologies, ensuring robustness. Sensitivity and Specificity were consolidated at 0.83 (95% confidence interval [CI]: 0.72-0.90) and 0.81 (95% CI: 0.73-0.88), respectively. The positive likelihood ratio and negative likelihood ratio were 4.45 (95% CI: 3.03-6.54) and 0.21 (95% CI: 0.12-0.35), respectively. The diagnostic odds ratio was 21.31 (95% CI: 10.25-44.30) and area under the receiver operating characteristic curve was 0.89 (95% CI: 0.86-0.91). Subgroup analysis highlighted significant variations in diagnostic accuracy by ethnicity and miRNA source, with non-Asian populations and serum-based tests showing higher diagnostic accuracy.
CONCLUSION
This meta-analysis demonstrated that circulating miRNAs hold substantial diagnostic value in distinguishing between benign and malignant lung nodules.
Topics: Humans; MicroRNAs; Sensitivity and Specificity; ROC Curve; Circulating MicroRNA; Lung
PubMed: 37986348
DOI: 10.1097/MD.0000000000035857 -
Scientific Reports Sep 2023Current clinical tests for Parkinson's disease (PD) provide insufficient diagnostic accuracy leading to an urgent need for improved diagnostic biomarkers. As microRNAs... (Meta-Analysis)
Meta-Analysis
Current clinical tests for Parkinson's disease (PD) provide insufficient diagnostic accuracy leading to an urgent need for improved diagnostic biomarkers. As microRNAs (miRNAs) are promising biomarkers of various diseases, including PD, this systematic review and meta-analysis aimed to assess the diagnostic accuracy of biofluid miRNAs in PD. All studies reporting data on miRNAs expression in PD patients compared to controls were included. Gene targets and significant pathways associated with miRNAs expressed in more than 3 biofluid studies with the same direction of change were analyzed using target prediction and enrichment analysis. A bivariate model was used to calculate sensitivity, specificity, likelihood ratios, and diagnostic odds ratio. While miR-24-3p and miR-214-3p were the most reported miRNA (7 each), miR-331-5p was found to be consistently up regulated in 4 different biofluids. Importantly, miR-19b-3p, miR-24-3p, miR-146a-5p, and miR-221-3p were reported in multiple studies without conflicting directions of change in serum and bioinformatic analysis found the targets of these miRNAs to be associated with pathways important in PD pathology. Of the 102 studies from the systematic review, 15 studies reported sensitivity and specificity data on combinations of miRNAs and were pooled for meta-analysis. Studies (17) reporting sensitivity and specificity data on single microRNA were pooled in a separate meta-analysis. Meta-analysis of the combinations of miRNAs (15 studies) showed that biofluid miRNAs can discriminate between PD patients and controls with good diagnostic accuracy (sensitivity = 0.82, 95% CI 0.76-0.87; specificity = 0.80, 95% CI 0.74-0.84; AUC = 0.87, 95% CI 0.83-0.89). However, we found multiple studies included more males with PD than any other group therefore possibly introducing a sex-related selection bias. Overall, our study captures key miRNAs which may represent a point of focus for future studies and the development of diagnostic panels whilst also highlighting the importance of appropriate study design to develop representative biomarker panels for the diagnosis of PD.
Topics: Male; Humans; MicroRNAs; Parkinson Disease; Biomarkers; Sensitivity and Specificity
PubMed: 37770507
DOI: 10.1038/s41598-023-43096-9 -
PloS One 2022The EBV-associated epithelial tumours consist 80% of all EBV-associated cancer, where the nasopharyngeal cancer (NPC) and EBV-associated gastric carcinoma (EBVaGC) are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The EBV-associated epithelial tumours consist 80% of all EBV-associated cancer, where the nasopharyngeal cancer (NPC) and EBV-associated gastric carcinoma (EBVaGC) are considered as the most frequent EBV-associated epithelial tumours. It has been shown that the BART-encoded miRNAs are abundantly expressed in EBV-associated epithelial tumours, hence, these miRNAs may serve as diagnostic and prognostic biomarkers for EBV-associated epithelial tumours. Therefore, the purpose of this systematic review and meta-analysis is to assess these EBV miRNAs as prognostic biomarkers for NPC and GC.
METHOD
This systematic review was developed based on PRISMA guidelines and utilizing PubMed, Web of Science, Scopus, Cochrane, and Google scholar databases. The retrieved articles were thoroughly screened in accordance with the selection criteria. The hazard ratio (HR) and 95% confidence interval (CI) for patient survival outcomes were used to evaluate EBV miRNA expression levels. To assess the risk of bias, funnel plot symmetry and Egger's bias test were employed.
RESULT
Eleven studies met the selection criteria for inclusion, and four were included in the meta-analysis. Most of the articles considered in this study were from China, with one study from South Korea. The overall pooled effect size estimation (HR) for upregulated EBV miRNAs was 3.168 (95% CI: 2.020-4.969), demonstrating that upregulated EBV miRNA expression enhanced the mortality risk in NPC and GC patients by three times.
CONCLUSION
To the best of our knowledge, this is the first meta-analysis that investigates the significance of EBV miRNAs as prognostic biomarkers in NPC and GC patients. The pooled effect estimates of HR of the various studies revealed that higher EBV miRNA expression in NPC and GC may result in a worse survival outcome. To assess the clinical significance of EBV miRNAs as prognostic biomarkers, larger-scale prospective studies are needed.
Topics: Biomarkers; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; MicroRNAs; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Prognosis
PubMed: 35436288
DOI: 10.1371/journal.pone.0266893 -
Genes Dec 2022: Chemoresistance is a significant barrier to combating head and neck cancer, and decoding this resistance can widen the therapeutic application of such chemotherapeutic... (Meta-Analysis)
Meta-Analysis
Clinical Investigation of Chemotherapeutic Resistance and miRNA Expressions in Head and Neck Cancers: A Thorough PRISMA Compliant Systematic Review and Comprehensive Meta-Analysis.
: Chemoresistance is a significant barrier to combating head and neck cancer, and decoding this resistance can widen the therapeutic application of such chemotherapeutic drugs. This systematic review and meta-analysis explores the influence of microRNA (miRNA) expressions on chemoresistance in head and neck cancers (HNC). The objective is to evaluate the theragnostic effects of microRNA expressions on chemoresistance in HNC patients and investigate the utility of miRNAs as biomarkers and avenues for new therapeutic targets. : We performed a comprehensive bibliographic search that included the SCOPUS, PubMed, and Science Direct bibliographic databases. These searches conformed to a predefined set of search strategies. Following the PRISMA guidelines, inclusion and exclusion criteria were framed upon completing the literature search. The data items extracted were tabulated and collated in MS Excel. This spreadsheet was used to determine the effect size estimation for the theragnostic effects of miRNA expressions on chemoresistance in HNC, the hazard ratio (HR), and 95% confidence intervals (95% CI). The comprehensive meta-analysis was performed using the random effects model. Heterogeneity among the data collected was assessed using the Q test, Tau, I, and Z measures. Publication bias of the included studies was checked using the Egger's bias indicator test, Orwin and classic fail-safe N test, Begg and Mazumdar rank collection test, and Duval and Tweedie's trim and fill methods. After collating the data from 23 studies, dysregulation of 34 miRNAs was observed in 2189 people. These data were gathered from 23 studies. Out of the 34 miRNAs considered, 22 were up-regulated, while 12 were down-regulated. The TaqMan transcription kits were the most used miRNA profiling platform, and miR-200c was seen to have a mixed dysregulation. We measured the overall pooled effect estimate of HR to be 1.516 for the various analyzed miRNA at a 95% confidence interval of 1.303-1.765, with a significant -value. The null hypothesis test's Z value was 5.377, and the -value was correspondingly noted to be less than 0.0001. This outcome indicates that the risk of death is determined to be higher in up-regulated groups than in down-regulated groups. Among the 34 miRNAs that were investigated, seven miRNAs were associated with an improved prognosis, especially with the overexpression of these seven miRNAs (miR15b-5p, miR-548b, miR-519d, miR-1278, miR-145, miR-200c, Hsa- miR139-3p). The findings reveal that intricate relationships between miRNAs' expression and chemotherapeutic resistance in HNC are more likely to exist and can be potential therapeutic targets. This review suggests the involvement of specific miRNAs as predictors of chemoresistance and sensitivity in HNC. The examination of the current study results illustrates the significance of miRNA expression as a theragnostic biomarker in medical oncology.
Topics: Humans; Biomarkers, Tumor; MicroRNAs; Head and Neck Neoplasms; Prognosis
PubMed: 36553594
DOI: 10.3390/genes13122325 -
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 -
Advanced Biology Jul 2023Extracellular vesicles (EVs) are emerging as biomarker candidates for early detection of prostate cancer. Studies compare EV-microRNA (miRNA) expression in individuals...
Extracellular vesicles (EVs) are emerging as biomarker candidates for early detection of prostate cancer. Studies compare EV-microRNA (miRNA) expression in individuals with prostate cancer (PCa) with cancer-free samples for diagnostic purposes. The aim of this study is to review miRNA signatures to investigate the overlap between miRNAs enriched in PCa tissue and miRNAs enriched in EVs isolated from subjects with PCa biofluids (i.e., urine, serum, and plasma). Signatures dysregulated in EVs from PCa biofluids and tissue are potentially associated with the primary tumor site and might be more indicative of PCa at an early stage. A systematic review of EV-derived miRNAs and a reanalysis of PCa tissue miRNA sequencing data for comparison is presented. Articles in the literature are screened for validated miRNA dysregulation in PCa and compared with TCGA primary PCa tumor data using DESeq2. This resulted in 190 dysregulated miRNAs being identified. Thirty-one eligible studies are identified, indicating 39 dysregulated EV-derived miRNAs. The top ten markers identified as significantly dysregulated in the PCa tissue dataset TCGA (e.g., miR-30b-3p, miR-210-3p, miR-126-3p, and miR-196a-5p) have a significant expression change in EVs with the same directionality in one or several statistically significant results. This analysis highlights several less frequently studied miRNAs in PCa literature.
Topics: Male; Humans; MicroRNAs; Prostatic Neoplasms; Extracellular Vesicles
PubMed: 37300338
DOI: 10.1002/adbi.202200327 -
Disease Markers 2022Colorectal cancer (CRC) is becoming increasingly prevalent worldwide. Fluoropyrimidine drugs are the primary chemotherapy regimens in routine clinical practice of CRC.... (Review)
Review
Colorectal cancer (CRC) is becoming increasingly prevalent worldwide. Fluoropyrimidine drugs are the primary chemotherapy regimens in routine clinical practice of CRC. However, the survival rate of patients on fluoropyrimidine-based chemotherapy varies significantly among individuals. Biomarkers of fluoropyrimidine drugs'' efficacy are needed to implement personalized medicine. This review summarized fluoropyrimidine drug-related microRNA (miRNA) by affecting metabolic enzymes or showing the relevance of drug efficacy. We first outlined 42 miRNAs that may affect the metabolism of fluoropyrimidine drugs. Subsequently, we filtered another 41 miRNAs related to the efficacy of fluoropyrimidine drugs based on clinical trials. Bioinformatics analysis showed that most well-established miRNA biomarkers were significantly enriched in the cancer pathways instead of the fluoropyrimidine drug metabolism pathways. The result also suggests that the miRNAs screened from metastasis patients have a more critical role in cancer development than those from non-metastasis patients. There are five miRNAs shared between these two lists. The miR-21, miR-215, and miR-218 can suppress fluoropyrimidine drugs'' catabolism. The miR-326 and miR-328 can reduce the efflux of fluoropyrimidine drugs. These five miRNAs could jointly act by increasing intracellular levels of fluoropyrimidine drugs'' cytotoxic metabolites, leading to better chemotherapy responses. In conclusion, we demonstrated that the dynamic changes in the transcriptional regulation via miRNAs might play significant roles in the efficacy and toxicity of the fluoropyrimidine drug. The reported miRNA biomarkers would help evaluate the efficacy of fluoropyrimidine drug-based chemotherapy and improve the prognosis of colorectal cancer patients.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Colorectal Neoplasms; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Prognosis
PubMed: 36051356
DOI: 10.1155/2022/1360954