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Advanced Science (Weinheim,... Aug 2023MicroRNAs (miRNAs) in extracellular vesicles (EVs) play essential roles in cancer initiation and progression. Quantitative measurements of EV miRNAs are critical for...
MicroRNAs (miRNAs) in extracellular vesicles (EVs) play essential roles in cancer initiation and progression. Quantitative measurements of EV miRNAs are critical for cancer diagnosis and longitudinal monitoring. Traditional PCR-based methods, however, require multi-step procedures and remain as bulk analysis. Here, the authors introduce an amplification-free and extraction-free EV miRNA detection method using a CRISPR/Cas13a sensing system. CRISPR/Cas13a sensing components are encapsulated in liposomes and delivered them into EVs through liposome-EV fusion. This allows for accurately quantify specific miRNA-positive EV counts using 1 × 10 EVs. The authors show that miR-21-5p-positive EV counts are in the range of 2%-10% in ovarian cancer EVs, which is significantly higher than the positive EV counts from the benign cells (<0.65%). The result show an excellent correlation between bulk analysis with the gold-standard method, RT-qPCR. The authors also demonstrate multiplexed protein-miRNA analysis in tumor-derived EVs by capturing EpCAM-positive EVs and quantifying miR-21-5p-positive ones in the subpopulation, which show significantly higher counts in the plasma of cancer patients than healthy controls. The developed EV miRNA sensing system provides the specific miRNA detection method in intact EVs without RNA extraction and opens up the possibility of multiplexed single EV analysis for protein and RNA markers.
Topics: Humans; MicroRNAs; Clustered Regularly Interspaced Short Palindromic Repeats; Extracellular Vesicles
PubMed: 37340600
DOI: 10.1002/advs.202301766 -
Plant Signaling & Behavior 2014MicroRNAs (miRNAs) control many aspects of development and adaption in plants and in animals by post-transcriptional control of mRNA stability and translatability. Over... (Review)
Review
MicroRNAs (miRNAs) control many aspects of development and adaption in plants and in animals by post-transcriptional control of mRNA stability and translatability. Over the last years numerous proteins have been identified in the miRNA pathway. The versatile scaffold protein RACK1 has been associated with efficient miRNA production and function in plants and metazoans. Here, we briefly summarize the differences of RACK1 function in the plant and animal miRNA pathways and discuss putative mechanisms and functional roles of RACK1 in miRNA biogenesis and action.
Topics: Animals; MicroRNAs; Models, Biological; Plants; Receptors for Activated C Kinase; Receptors, Cell Surface; Signal Transduction
PubMed: 24521556
DOI: 10.4161/psb.27909 -
Current Cardiology Reports Feb 2024MicroRNAs (miRNAs)-short, non-coding RNAs-play important roles in almost all aspects of cardiovascular biology, and changes in intracellular miRNA expression are... (Review)
Review
PURPOSE OF REVIEW
MicroRNAs (miRNAs)-short, non-coding RNAs-play important roles in almost all aspects of cardiovascular biology, and changes in intracellular miRNA expression are indicative of cardiovascular disease development and progression. Extracellular miRNAs, which are easily measured in blood and can be reflective of changes in intracellular miRNA levels, have emerged as potential non-invasive biomarkers for disease. This review summarizes current knowledge regarding miRNAs as biomarkers for assessing cardiovascular disease risk and prognosis.
RECENT FINDINGS
Numerous studies over the last 10-15 years have identified associations between extracellular miRNA profiles and cardiovascular disease, supporting the potential use of extracellular miRNAs as biomarkers for risk stratification. However, clinical application of extracellular miRNA profiles has been hampered by poor reproducibility and inter-study variability that is due largely to methodological differences between studies. While recent studies indicate that circulating extracellular miRNAs are promising biomarkers for cardiovascular disease, evidence for clinical implementation is lacking. This highlights the need for larger, well-designed studies that use standardized methods for sample preparation, miRNA isolation, quantification, and normalization.
Topics: Humans; MicroRNAs; Cardiovascular Diseases; Reproducibility of Results; Prognosis; Biomarkers
PubMed: 38206553
DOI: 10.1007/s11886-023-02014-1 -
BioMed Research International 2015MicroRNAs (miRNAs) play an essential role in the onset and development of many cardiovascular diseases. Increasing evidence shows that miRNAs can be used as potential... (Review)
Review
MicroRNAs (miRNAs) play an essential role in the onset and development of many cardiovascular diseases. Increasing evidence shows that miRNAs can be used as potential diagnostic biomarkers for cardiovascular diseases, and miRNA-based therapy may be a promising therapy for the treatment of cardiovascular diseases. The microRNA-143/-145 (miR-143/-145) cluster is essential for differentiation of vascular smooth muscle cells (VSMCs) and determines VSMC phenotypic switching. In this review, we summarize the recent progress in knowledge concerning the function of miR-143/-145 in the cardiovascular system and their role in cardiovascular diseases. We discuss the potential role of miR-143/-145 as valuable biomarkers for cardiovascular diseases and explore the potential strategy of targeting miR-143 and miR-145.
Topics: Animals; Biomarkers; Cardiovascular Diseases; Humans; MicroRNAs; Models, Biological; Molecular Targeted Therapy
PubMed: 26221598
DOI: 10.1155/2015/531740 -
Genes Mar 2022A review of miRNA (microRNA) profiling studies in keratoconus. (Review)
Review
AIM
A review of miRNA (microRNA) profiling studies in keratoconus.
METHODS
Literature search strategy-PubMed central database, using miRNA or microRNA and keratoconus as keywords.
RESULTS
Eleven experimental or clinical studies on humans regarding miRNA and keratoconus, published in English between 2009 and 2020 were retrieved.
CONCLUSION
The publications regarding the role of miRNAs in keratoconus are scarce and diverse but provide some valuable information about potential new mechanisms of keratoconus development and progression. The cornea expresses almost 300 different miRNAs, 18 of which are specific, and miR-184 is by far the most abundant, with expression restricted to central basal and suprabasal epithelial cells. Mutations in the seed region of were proved to be rare and nonspecific in patients with isolated keratoconus. Overall, in keratoconus, a total of 29 miRNAs were upregulated, and 11 were downregulated. It appeared that miR-143-3p, miR-182-5p, and miR-92a-3p were highly expressed, while the miRNAs connected to cell-cell junction, cell division, and motor activity were downregulated. In less advanced forms, altered expression of four miRNAs-miR-151a-3p, miR-194-5p, miR-195-5p, miR-185-5p-was proved in the cone epithelium; in contrast, in advanced keratoconus, the expression of miR-151a-3p and miR-194-5p remained altered, changes in the expression of miR-195 and miR-185 were not reported, and the expression of miR-138-5p, miR-146b-5p, miR-28-5p, and miR-181a-2-3p was also altered in the corneal epithelium. Keratoconus is a dynamic process of corneal stromal thinning that might result from a dynamic miRNA expression in the corneal epithelium exposed to environmental and behavioral factors causing repetitive traumas. Further experimental studies are needed to prove this hypothesis.
Topics: Biomarkers; Epithelium, Corneal; Humans; Keratoconus; MicroRNAs
PubMed: 35456395
DOI: 10.3390/genes13040588 -
The FEBS Journal Nov 2009In recent years, our understanding of how gene regulatory networks control cell physiology has improved dramatically. Studies have demonstrated that transcription is... (Review)
Review
In recent years, our understanding of how gene regulatory networks control cell physiology has improved dramatically. Studies have demonstrated that transcription is regulated not only by protein factors, but also by small RNA molecules, microRNAs (miRNAs). The first miRNA was discovered in 1993 as a result of a genetic screen for mutations in Caenorhabditis elegans. Since then, the use of sophisticated techniques and screening tools has promoted a more definitive understanding of the role of miRNAs in mammalian development and diseases. miRNAs have emerged as important regulators of genes involved in many biological processes, including development, cell proliferation and differentiation, apoptosis and metabolism. Over the last few years, the number of reviews dealing with miRNAs has increased at an impressive pace. In this review, we present general information on miRNA biology and focus more closely on comparing the expression, regulation and molecular functions of the two miRNAs, miR-375 and miR-124a. miR-375 and miR-124a share similar features; they are both specifically expressed in the pancreas and brain and directly bind a common target gene transcript encoding myotrophin, which regulates exocytosis and hormone release. Here, we summarize the available data obtained by our group and other laboratories and provide an overview of the specific molecular function of miR-375 and miR-124a in the pancreas and the brain, revealing a potential functional overlap for these two miRNAs and the emerging therapeutic potential of miRNAs in the treatment of human metabolic diseases.
Topics: Animals; Brain; Humans; MicroRNAs; Models, Biological; Pancreas
PubMed: 20102393
DOI: 10.1111/j.1742-4658.2009.07353.x -
Biomedicine & Pharmacotherapy =... Dec 2018MicroRNAs can exhibit opposite functions in different tumors. MiR-31 is a representative example as it can not only enhance tumor development and progression in... (Review)
Review
MicroRNAs can exhibit opposite functions in different tumors. MiR-31 is a representative example as it can not only enhance tumor development and progression in pancreatic cancer, colorectal cancer and so on, but also inhibit tumorigenesis and induce apoptosis in ovarian cancer, prostate cancer and etc. The mechanism underlying its' pleiotropy remains unknown. Several recent studies that focused on the global gene expression changes caused by aberrant miR-31 provided information on the upstream and downstream events associated with deregulated miR-31. MiR-31 might interact with a number of signaling pathways including RAS/MARK, PI3K/AKT and RB/E2F to play its opposite functions. This review summarizes the target genes and pathways associated with miR-31 and examines the mechanisms underlying the function of miR-31. The resulting hypothesis is possible that the tissue-specific features of adenocarcinoma and squamous cell cancer and the positive feedback loop consists of miR-31 and its upstream and downstream may account for the diversity of miR-31 functions.
Topics: Carcinogens; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Humans; MicroRNAs; Neoplasms
PubMed: 30372817
DOI: 10.1016/j.biopha.2018.09.132 -
RNA (New York, N.Y.) Jun 2018The emergence of microRNA as regulators of organogenesis and tissue differentiation has stimulated interest in the ablation of microRNA expression and function during...
The emergence of microRNA as regulators of organogenesis and tissue differentiation has stimulated interest in the ablation of microRNA expression and function during discrete periods of development. To this end, inducible, conditional modulation of microRNA expression with doxycycline-based tetracycline-controlled transactivator and tamoxifen-based estrogen receptor systems has found widespread use. However, the induction agents and components of genome recombination systems negatively impact pregnancy, parturition, and postnatal development; thereby limiting the use of these technologies between late gestation and the early postnatal period. MicroRNA inhibitor (antimiR) administration also represents a means of neutralizing microRNA function in vitro and in vivo. To date, these studies have used direct (parenteral) administration of antimiRs to experimental animals. As an extension of this approach, an alternative means of regulating microRNA expression and function is described here: the maternal-placental-fetal transmission of antimiRs. When administered to pregnant dams, antimiRs were detected in offspring and resulted in a pronounced and persistent reduction in detectable steady-state free microRNA levels in the heart, kidney, liver, lungs, and brain. This effect was comparable to direct injection of newborn mouse pups with antimiRs, although maternal delivery resulted in fewer off-target effects. Furthermore, depletion of steady-state microRNA levels via the maternal route resulted in concomitant increases in steady-state levels of selected microRNA targets. This novel methodology permits the temporal regulation of microRNA function during late gestation and in neonates, without recourse to conventional approaches that rely on doxycycline and tamoxifen, which may confound studies on developmental processes.
Topics: Animals; Animals, Newborn; Female; Fetus; Maternal-Fetal Exchange; Mice; Mice, Inbred C57BL; MicroRNAs; NIH 3T3 Cells; Placenta; Pregnancy
PubMed: 29540511
DOI: 10.1261/rna.063206.117 -
Best Practice & Research. Clinical... Oct 2016miRNA-guided diagnostics is a powerful molecular approach for evaluating clinical samples through miRNA detection and/or visualization. To date, this approach has been... (Review)
Review
miRNA-guided diagnostics is a powerful molecular approach for evaluating clinical samples through miRNA detection and/or visualization. To date, this approach has been successfully used to diagnose, manage, and/or monitor a wide range of neoplastic and non-neoplastic diseases. Despite the promise of miRNA-guided diagnostics, particularly in the field of minimally invasive biomarkers, several knowledge and practical issues confound or hinder translation into routine clinical practice including: miRNA sequence database errors, suboptimal RNA extraction methods, detection assay variability, a vast array of online resources for bioinformatic analyses, and non-standardized statistical analyses for miRNA clinical testing. In this review, we raise awareness of these issues and recommend research directions to help specialists in endocrinology and metabolism integrate miRNA testing into clinical decision-making.
Topics: Biomarkers; Humans; MicroRNAs; Molecular Diagnostic Techniques
PubMed: 27923451
DOI: 10.1016/j.beem.2016.07.002 -
Molecular Cancer May 2013MicroRNAs(miRNA) are noncoding RNAs of about 19-23 nucleotides that are crucial for many biological processes. Members of the microRNA-148/152(miR-148/152) family, which... (Review)
Review
MicroRNAs(miRNA) are noncoding RNAs of about 19-23 nucleotides that are crucial for many biological processes. Members of the microRNA-148/152(miR-148/152) family, which include microRNA-148a(miR-148a), microRNA-148b(miR-148b), and microRNA-152(miR-152), are expressed differently in tumor and nontumor tissues and are involved in the genesis and development of disease. Furthermore, members of the miR-148/152 family are important in the growth and development of normal tissues. Members of the miR-148/152 family regulate target genes and are regulated by methylation of CPG islands. In this review, we report recent studies on the expression of members of the miR-148/152 family, methylation of CPG islands, and their target genes in different diseases, as well as in normal tissues.
Topics: DNA Methylation; Gene Expression Regulation; Humans; MicroRNAs; Multigene Family; Nucleic Acid Conformation; Organ Specificity
PubMed: 23683438
DOI: 10.1186/1476-4598-12-43