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Clinical Gastroenterology and... Apr 2022Intestinal strictures are a common complication of Crohn's disease (CD). Biomarkers of intestinal strictures would assist in their prediction, diagnosis, and monitoring....
BACKGROUND AND AIMS
Intestinal strictures are a common complication of Crohn's disease (CD). Biomarkers of intestinal strictures would assist in their prediction, diagnosis, and monitoring. Herein we provide a comprehensive systematic review of studies assessing biomarkers that may predict or diagnose CD-associated strictures.
METHODS
We performed a systematic review of PubMed, EMBASE, ISI Web of Science, Cochrane Library, and Scopus to identify citations pertaining to biomarkers of intestinal fibrosis through July 6, 2020, that used a reference standard of full-thickness histopathology or cross-sectional imaging or endoscopy. Studies were categorized based on the type of biomarker they evaluated (serum, genetic, histopathologic, or fecal).
RESULTS
Thirty-five distinct biomarkers from 3 major groups were identified: serum (20 markers), genetic (9 markers), and histopathology (6 markers). Promising markers include cartilage oligomeric matrix protein, hepatocyte growth factor activator, and lower levels of microRNA-19-3p (area under the curves were 0.805, 0.738, and 0.67, respectively), and multiple anti-flagellin antibodies (A4-Fla2 [odds ratio, 3.41], anti Fla-X [odds ratio, 2.95], and anti-CBir1 [multiple]). Substantial heterogeneity was observed and none of the markers had undergone formal validation. Specific limitations to acceptance of these markers included failure to use a standardized definition of stricturing disease, lack of specificity, and insufficient relevance to the pathogenesis of intestinal strictures or incomplete knowledge regarding their operating properties.
CONCLUSIONS
There is a lack of well-defined studies on biomarkers of intestinal stricture. Development of reliable and accurate biomarkers of stricture is a research priority. Biomarkers can support the clinical management of CD patients and aid in the stratification and monitoring of patients during clinical trials of future antifibrotic drug candidates.
Topics: Biomarkers; Cartilage Oligomeric Matrix Protein; Constriction, Pathologic; Crohn Disease; Humans; Intestinal Obstruction; MicroRNAs; Serine Endopeptidases
PubMed: 34089850
DOI: 10.1016/j.cgh.2021.05.054 -
Genes Aug 2021SALL4 is a zinc finger transcription factor that belongs to the spalt-like (SALL) gene family. It plays important roles in the maintenance of self-renewal and...
SALL4 is a zinc finger transcription factor that belongs to the spalt-like (SALL) gene family. It plays important roles in the maintenance of self-renewal and pluripotency of embryonic stem cells, and its expression is repressed in most adult organs. SALL4 re-expression has been observed in different types of human cancers, and dysregulation of SALL4 contributes to the pathogenesis, metastasis, and even drug resistance of multiple cancer types. Surprisingly, little is known regarding how SALL4 expression is controlled, but recently microRNAs (miRNAs) have emerged as important regulators of SALL4. Due to the ability of regulating targets differentially in specific tissues, and recent advances in systemic and organ specific miRNA delivery mechanisms, miRNAs have emerged as promising therapeutic targets for cancer treatment. In this review, we summarize current knowledge of the interaction between SALL4 and miRNAs in mammalian development and cancer, paying particular attention to the emerging roles of the Let-7/Lin28 axis. In addition, we discuss the therapeutic prospects of targeting SALL4 using miRNA-based strategies, with a focus on the Let-7/LIN28 axis.
Topics: Animals; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Gene Expression Regulation, Developmental; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms; Lung Neoplasms; MicroRNAs; Transcription Factors
PubMed: 34573282
DOI: 10.3390/genes12091301 -
Non-coding RNA Jul 2023MicroRNAs (miRNAs) perform a pivotal role in the regulation of gene expression across the animal kingdom. As negative regulators of gene expression, miRNAs have been... (Review)
Review
MicroRNAs (miRNAs) perform a pivotal role in the regulation of gene expression across the animal kingdom. As negative regulators of gene expression, miRNAs have been shown to function in the genetic pathways that control many biological processes and have been implicated in roles in human disease. First identified as an aging-associated gene in , miR-71, a miRNA, has a demonstrated capability of regulating processes in numerous different invertebrates, including platyhelminths, mollusks, and insects. In these organisms, miR-71 has been shown to affect a diverse range of pathways, including aging, development, and immune response. However, the exact mechanisms by which miR-71 regulates these pathways are not completely understood. In this paper, we review the identified functions of miR-71 across multiple organisms, including identified gene targets, pathways, and the conditions which affect regulatory action. Additionally, the degree of conservation of miR-71 in the evaluated organisms and the conservation of their predicted binding sites in target 3' UTRs was measured. These studies may provide an insight on the patterns, interactions, and conditions in which miR-71 is able to exert genotypic and phenotypic influence.
PubMed: 37624033
DOI: 10.3390/ncrna9040041 -
Medicina (Kaunas, Lithuania) Mar 2022Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are rare atypical parkinsonian syndromes, characterized by motor and cognitive symptoms. Their... (Review)
Review
Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are rare atypical parkinsonian syndromes, characterized by motor and cognitive symptoms. Their clinical diagnosis is challenging because there are no established biomarkers. Dysregulation of microRNAs (miRNAs/miRs) has been reported to serve an important role in neurodegenerative diseases. However, the miRNA profiles of MSA and PSP patients are rarely reported. The aim of this study was to critically review the role of miRNAs as diagnostic biomarkers to differentiate these atypical parkinsonian disorders and their role in disease pathogenesis. A systematic literature search of PubMed was conducted up to February 2022 according the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 15 studies were analyzed. Three studies have shown that miR-9-3p, miR-19a, miR-19b, and miR-24 are potential biomarkers for MSA. In two studies, miR-132 was downregulated, whereas miR-147a and miR-518e were upregulated in the brain tissue of PSP patients. The potential of miRNA is still uncertain as a potential differential diagnostic marker to identify these disorders. Pre-analytical and analytical factors of included studies were important limitations to justify the introduction of miRNAs into clinical practice.
Topics: Biomarkers; Humans; MicroRNAs; Multiple System Atrophy; Parkinsonian Disorders; Supranuclear Palsy, Progressive
PubMed: 35454322
DOI: 10.3390/medicina58040483 -
Cancers Jul 2023Differentiating glioma from primary central nervous system lymphoma (PCNSL) can be challenging, and current diagnostic measures such as MRI and biopsy are of limited... (Review)
Review
Differentiating glioma from primary central nervous system lymphoma (PCNSL) can be challenging, and current diagnostic measures such as MRI and biopsy are of limited efficacy. Liquid biopsies, which detect circulating biomarkers such as microRNAs (miRs), may provide valuable insights into diagnostic biomarkers for improved discrimination. This review aimed to investigate the role of specific miRs in diagnosing and differentiating glioma from PCNSL. A systematic search was conducted of PubMed, Scopus, Web of Science, and Embase for articles on liquid biopsies as a diagnostic method for glioma and PCNSL. Sixteen dysregulated miRs were identified with significantly different levels in glioma and PCNSL, including miR-21, which was the most prominent miR with higher levels in PCNSL, followed by glioma, including glioblastoma (GBM), and control groups. The lowest levels of miR-16 and miR-205 were observed in glioma, followed by PCNSL and control groups, whereas miR-15b and miR-301 were higher in both tumor groups, with the highest levels observed in glioma patients. The levels of miR-711 were higher in glioma (including GBM) and downregulated in PCNSL compared to the control group. This review suggests that using these six circulating microRNAs as liquid biomarkers with unique changing patterns could aid in better discrimination between glioma, especially GBM, and PCNSL.
PubMed: 37509289
DOI: 10.3390/cancers15143628 -
Brain Research Bulletin Mar 2023MicroRNAs (miRNAs) exhibit a crucial role in the pathogenesis and progress of neurodegenerative disorders. Recent studies have shown abnormal levels of miRNA expression... (Meta-Analysis)
Meta-Analysis Review
MicroRNAs (miRNAs) exhibit a crucial role in the pathogenesis and progress of neurodegenerative disorders. Recent studies have shown abnormal levels of miRNA expression in patients with amyotrophic lateral sclerosis (ALS). Clinical data also confirmed that miRNAs in these patients are inconsistent across studies. A comprehensive systematic review and meta-analysis of current studies can help recognize the important roles of miRNAs during ALS development. Therefore, we initially aimed to perform a systematic literature review on the muscle or serum miRNAs in patients with ALS and healthy individuals. Subsequently, we quantitatively summarized the clinical data of muscle or serum miRNA of patients with ALS and healthy individuals using a meta-analytical technique. 11 studies comprising 281 patients with ALS and 244 healthy control (HC) controls were identified from PubMed and Web of Science for meta-analysis. A systematic review revealed that miRNA levels are closely associated with the occurrence of ALS disease. The expression levels of the most relevant miRNAs were either increased or decreased. The random-effects meta-analysis indicated that the levels of miR-206, miR-133b, and miR-338-3p were significantly elevated in patients with ALS than in HC subjects. By contrast, there was no significant differences in the miR-133a levels between patients with ALS and HC subjects. Collectively, our outcomes demonstrated that serum miR-206, miR-133b, and miR-338-3p were significantly increased in patients with ALS. We speculated that the increased expression levels of miR-206, miR-133b and miR-338-3p are potential promising biomarkers for ALS.
Topics: Humans; MicroRNAs; Amyotrophic Lateral Sclerosis; Biomarkers
PubMed: 36681253
DOI: 10.1016/j.brainresbull.2023.01.005 -
Biomedicines Feb 2023MicroRNAs (miRNAs) are involved in the regulation of mitochondrial function and homeostasis, and in the modulation of cell metabolism, by targeting known oncogenes and... (Review)
Review
MicroRNAs (miRNAs) are involved in the regulation of mitochondrial function and homeostasis, and in the modulation of cell metabolism, by targeting known oncogenes and tumor suppressor genes of metabolic-related signaling pathways involved in the hallmarks of cancer. This systematic review focuses on articles describing the role, association, and/or involvement of miRNAs in regulating the mitochondrial function and metabolic reprogramming of cancer cells. Following the PRISMA guidelines, the articles reviewed were published from January 2010 to September 2022, with the search terms "mitochondrial microRNA" and its synonyms (mitochondrial microRNA, mitochondrial miRNA, mito microRNA, or mitomiR), "reprogramming metabolism," and "cancer" in the title or abstract). Thirty-six original research articles were selected, revealing 51 miRNAs with altered expression in 12 cancers: bladder, breast, cervical, colon, colorectal, liver, lung, melanoma, osteosarcoma, pancreatic, prostate, and tongue. The actions of miRNAs and their corresponding target genes have been reported mainly in cell metabolic processes, mitochondrial dynamics, mitophagy, apoptosis, redox signaling, and resistance to chemotherapeutic agents. Altogether, these studies support the role of miRNAs in the metabolic reprogramming hallmark of cancer cells and highlight their potential as predictive molecular markers of treatment response and/or targets that can be used for therapeutic intervention.
PubMed: 36979672
DOI: 10.3390/biomedicines11030693 -
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 -
Biomolecules Dec 2021Oral cancer is a significant public health issue, being the eighth most common cancer worldwide with over 300,000 cases diagnosed annually. Early diagnosis and adequate... (Review)
Review
Oral cancer is a significant public health issue, being the eighth most common cancer worldwide with over 300,000 cases diagnosed annually. Early diagnosis and adequate management of oral potentially malignant disorders (OPMDs) before transformation into oral squamous cell carcinoma (OSCC) is critical to reduce deaths, morbidity, and to improve overall prognosis. MicroRNAs (miRNAs) are small noncoding RNAs involved in the post-transcriptional regulation of protein expression and implicated in the control of numerous cellular pathways and impacting physiological, developmental, and pathological processes. Dysregulation of miRNAs has been reported in many cancers and has been demonstrated to play a critical role in cancer initiation, progression, apoptosis, invasion and metastasis. This systematic review provides a comprehensive summary of the prevailing literature on miRNA signatures in OPMDs, specifically leukoplakia with or without oral epithelial dysplasia, and their utility in predicting malignant transformation into OSCC. Eighteen articles describing 73 unique and differentially expressed microRNAs met the criteria for inclusion in this review. We reviewed the characteristics and methodology for each of these studies and assessed the sensitivity and specificity of the studied miRNAs in predicting malignant transformation. This systematic review highlights the significant interest in miRNAs and their tremendous potential as prognostic markers for predicting the malignant transformation of OPMDs into OSCC.
Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease Progression; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Leukoplakia, Oral; MicroRNAs; Mouth Neoplasms
PubMed: 34944523
DOI: 10.3390/biom11121879 -
Journal of Cerebral Blood Flow and... Jun 2022This systematic review aimed to establish the range and quality of clinical and preclinical evidence supporting the association of individual microRNAs, and the use of...
This systematic review aimed to establish the range and quality of clinical and preclinical evidence supporting the association of individual microRNAs, and the use of microRNA expression in the diagnosis and prognosis of ischaemic or haemorrhagic stroke. Electronic databases were searched from 1993 to October 2021, using key words relevant to concepts of stroke and microRNA. Studies that met specific inclusion and exclusion criteria were selected for data extraction. To minimise erroneous associations, findings were restricted to microRNAs reported to change in more than two independent studies. Of the papers assessed, 155 papers reported a change in microRNA expression observed in more than two independent studies. In ischaemic studies, two microRNAs were consistently differentially expressed in clinical samples (miR-29b & miR-146a) and four were altered in preclinical samples (miR-137, miR-146a, miR-181b & miR-223-3p). Across clinical and preclinical haemorrhagic studies, four microRNAs were downregulated consistently (miR-26a, miR-126, miR-146a & miR-155). Across included studies, miR-126 and miR-146a were the only two microRNAs to be differentially expressed in clinical and preclinical cohorts following ischaemic or haemorrhagic stroke. Further studies, employing larger populations with consistent methodologies, are required to validate the true clinical value of circulating microRNAs as biomarkers of ischaemic and haemorrhagic stroke.
Topics: Biomarkers; Circulating MicroRNA; Hemorrhagic Stroke; Humans; MicroRNAs; Stroke
PubMed: 35240874
DOI: 10.1177/0271678X221085090