-
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 -
Journal of Cardiology Jan 2016Atherosclerosis is a chronic inflammatory disease of the arterial wall. It is characterized by subendothelial accumulation of low-density lipoprotein cholesterol, and... (Review)
Review
Atherosclerosis is a chronic inflammatory disease of the arterial wall. It is characterized by subendothelial accumulation of low-density lipoprotein cholesterol, and its subsequent modification at athero-prone areas leads to further activation of the vascular wall and maintains vascular inflammation. An entirely new level of post-transcriptional gene regulation through microRNA (miR) expression has emerged recently as an important mechanism in the development and progression of numerous diseases, including atherosclerosis. Recently, miR-33a/b have been shown to act as post-transcriptional regulators of lipid metabolism, and their pharmacological inhibition diminished atherosclerosis by raising plasma high-density lipoprotein levels. This review summarizes the current understanding of the functions of miR-33a/b and the progress in miRNA therapeutics for treatment of various diseases, including atherosclerosis.
Topics: Atherosclerosis; Cholesterol, HDL; Humans; Lipid Metabolism; MicroRNAs
PubMed: 26645139
DOI: 10.1016/j.jjcc.2015.10.017 -
Molecules and Cells Jan 2023MicroRNAs (miRNAs) play cardinal roles in regulating biological pathways and processes, resulting in significant physiological effects. To understand the complex... (Review)
Review
MicroRNAs (miRNAs) play cardinal roles in regulating biological pathways and processes, resulting in significant physiological effects. To understand the complex regulatory network of miRNAs, previous studies have utilized massivescale datasets of miRNA targeting and attempted to computationally predict the functional targets of miRNAs. Many miRNA target prediction tools have been developed and are widely used by scientists from various fields of biology and medicine. Most of these tools consider seed pairing between miRNAs and their mRNA targets and additionally consider other determinants to improve prediction accuracy. However, these tools exhibit limited prediction accuracy and high false positive rates. The utilization of additional determinants, such as RNA modifications and RNA-binding protein binding sites, may further improve miRNA target prediction. In this review, we discuss the determinants of functional miRNA targeting that are currently used in miRNA target prediction and the potentially predictive but unappreciated determinants that may improve prediction accuracy.
Topics: Computational Biology; MicroRNAs; RNA, Messenger; Gene Targeting
PubMed: 36697234
DOI: 10.14348/molcells.2023.2157 -
Biomedicine & Pharmacotherapy =... May 2023MicroRNA production in tumorigenesis is dysregulated by a variety of processes, such as proliferation and removal of microRNA genes, aberrant transcriptional regulation... (Review)
Review
MicroRNA production in tumorigenesis is dysregulated by a variety of processes, such as proliferation and removal of microRNA genes, aberrant transcriptional regulation of microRNAs, disrupted epigenetic alterations, and failures in the miRNA biogenesis machinery. Under some circumstances, miRNAs may act as tumorigenic and maybe anti-oncogenes. Tumor aspects such as maintaining proliferating signals, bypassing development suppressors, delaying apoptosis, stimulating metastasis and invasion, and promoting angiogenesis have been linked to dysfunctional and dysregulated miRNAs. MiRNAs have been found as possible biomarkers for human cancer in a great deal of research, which requires additional evaluation and confirmation. It is known that hsa-miR-28 can function as an oncogene or tumor suppressor in many malignancies, and it does this by modulating the expression of several genes and the downstream signaling network. MiR-28-5p and miR-28-3p, which originate from the same RNA hairpin precursor miR-28, have essential roles in a variety of cancers. This review outlines the function and mechanisms of miR-28-3p and miR-28-5p in human cancers and illustrates the miR-28 family's potential utility as a diagnostic biomarker for prognosis and early detection of cancers.
Topics: Humans; MicroRNAs; Neoplasms; Gene Expression Regulation; Oncogenes
PubMed: 36868012
DOI: 10.1016/j.biopha.2023.114453 -
Genes & Development Jul 2023MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that play critical roles in development and disease. Target-directed miRNA degradation (TDMD),...
MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that play critical roles in development and disease. Target-directed miRNA degradation (TDMD), a pathway in which miRNAs that bind to specialized targets with extensive complementarity are rapidly decayed, has emerged as a potent mechanism of controlling miRNA levels. Nevertheless, the biological role and scope of miRNA regulation by TDMD in mammals remains poorly understood. To address these questions, we generated mice with constitutive or conditional deletion of , which encodes an essential TDMD factor. Loss of resulted in developmental defects in the heart and lungs, growth restriction, and perinatal lethality. Small RNA sequencing of embryonic tissues revealed widespread miRNA regulation by TDMD and greatly expanded the known catalog of miRNAs regulated by this pathway. These experiments also uncovered novel features of TDMD-regulated miRNAs, including their enrichment in cotranscribed clusters and examples in which TDMD underlies "arm switching," a phenomenon wherein the dominant strand of a miRNA precursor changes in different tissues or conditions. Importantly, deletion of two miRNAs, miR-322 and miR-503, rescued growth of -null embryos, directly implicating the TDMD pathway as a regulator of mammalian body size. These data illuminate the broad landscape and developmental role of TDMD in mammals.
Topics: Mice; Animals; MicroRNAs; Mammals; Base Sequence
PubMed: 37553261
DOI: 10.1101/gad.350906.123 -
Current Rheumatology Reports Aug 2016Micro ribonucleic acid (microRNA) regulation and expression has become an emerging field in determining the mechanisms regulating a variety of inflammation-mediated... (Review)
Review
Micro ribonucleic acid (microRNA) regulation and expression has become an emerging field in determining the mechanisms regulating a variety of inflammation-mediated diseases. Several studies have focused on specific microRNAs that are differentially expressed in cases of osteoarthritis. Furthermore, several targets of these miRNAs important in disease progression have also been identified. In this review, we focus on microRNA biogenesis, regulation, detection, and quantification with an emphasis on cellular localization and how these concepts may be linked to disease processes such as osteoarthritis. Next, we review the relationships of specific microRNAs to certain features and risk factors associated with osteoarthritis such as inflammation, obesity, autophagy, and cartilage homeostasis. We also identify certain microRNAs that are differentially expressed in osteoarthritis but have unidentified targets and functions in the disease state. Lastly, we identify the potential use of microRNAs for therapeutic purposes and also mention certain remedies that regulate microRNA expression.
Topics: Cartilage, Articular; Inflammation; Intracellular Signaling Peptides and Proteins; MicroRNAs; Osteoarthritis
PubMed: 27402113
DOI: 10.1007/s11926-016-0604-x -
Viruses Jun 2022Herpesviruses are ubiquitous human pathogens. After productive (lytic) infection, all human herpesviruses are able to establish life-long latent infection and reactivate... (Review)
Review
Herpesviruses are ubiquitous human pathogens. After productive (lytic) infection, all human herpesviruses are able to establish life-long latent infection and reactivate from it. Latent infection entails suppression of viral replication, maintenance of the viral genome in infected cells, and the ability to reactivate. Most human herpesviruses encode microRNAs (miRNAs) that regulate these processes during latency. Meanwhile, cellular miRNAs are hijacked by herpesviruses to participate in these processes. The viral or cellular miRNAs either directly target viral transcripts or indirectly affect viral infection through host pathways. These findings shed light on the molecular determinants that control the lytic-latent switch and may lead to novel therapeutics targeting latent infection. We discuss the multiple mechanisms by which miRNAs regulate herpesvirus latency, focusing on the patterns in these mechanisms.
Topics: Gene Expression Regulation, Viral; Herpesvirus 8, Human; Humans; Latent Infection; MicroRNAs; Virus Latency; Virus Replication
PubMed: 35746686
DOI: 10.3390/v14061215 -
FEBS Letters Jun 2018MicroRNAs (miRNAs) are evolutionarily conserved small regulatory RNAs that participate in the adjustment of many, if not all, fundamental biological processes. Molecular... (Review)
Review
MicroRNAs (miRNAs) are evolutionarily conserved small regulatory RNAs that participate in the adjustment of many, if not all, fundamental biological processes. Molecular mechanisms involved in miRNA biogenesis and mode of action have been elucidated in the past two decades. Similar to many cellular pathways, miRNA processing and function can be globally or specifically regulated at several levels and by numerous proteins and RNAs. Given their role as fine-tuning molecules, it is essential for miRNA expression to be tightly regulated in order to maintain cellular homeostasis. Here, we review our current knowledge of the first step of their maturation occurring in the nucleus and how it can be specifically and dynamically modulated.
Topics: Animals; Cell Nucleus; Gene Expression Regulation; Homeostasis; Humans; MicroRNAs; Models, Molecular; RNA Polymerase II; Ribonuclease III
PubMed: 29683487
DOI: 10.1002/1873-3468.13067 -
Briefings in Bioinformatics Jul 2020Rapid advances in genomics discovery tools and a growing realization of microRNA's implication in intercellular communication have led to a proliferation of studies of... (Review)
Review
Rapid advances in genomics discovery tools and a growing realization of microRNA's implication in intercellular communication have led to a proliferation of studies of circulating microRNA sorting and regulation across cells and different species. Although sometimes, reaching controversial scientific discoveries and conclusions, these studies have yielded new insights in the functional roles of circulating microRNA and a plethora of analytical methods and tools. Here, we consider this body of work in light of key computational principles underpinning discovery of circulating microRNAs in terms of their sorting and targeting, with the goal of providing practical guidance for applications that is focused on the design and analysis of circulating microRNAs and their context-dependent regulation. We survey a broad range of informatics methods and tools that are available to the researcher, discuss their key features, applications and various unsolved problems and close this review with prospects and broader implication of this field.
Topics: Biological Transport; Computational Biology; Gene Regulatory Networks; MicroRNAs
PubMed: 31504144
DOI: 10.1093/bib/bbz079 -
Current Opinion in Structural Biology Oct 2022MicroRNAs are prevalent regulators of gene expression, controlling most of the proteome in multicellular organisms. To generate the functional small RNAs, precise... (Review)
Review
MicroRNAs are prevalent regulators of gene expression, controlling most of the proteome in multicellular organisms. To generate the functional small RNAs, precise processing steps are required. In animals, microRNA biogenesis is initiated by Microprocessor that minimally consists of the Drosha enzyme and its partner, DGCR8. This first step is critical for selecting primary microRNAs, and many RNA-binding proteins and regulatory pathways target both the accuracy and efficiency of microRNA maturation. Structures of Drosha and DGCR8 in complex with primary microRNAs elucidate how RNA structural features rather than sequence provide the framework for substrate recognition. Comparing multiple states of Microprocessor and the closely related Dicer homologs shed light on the dynamic protein-RNA complex assembly and disassembly required to recognize RNAs with diverse sequences via common structural features.
Topics: Animals; MicroRNAs; Proteome; RNA Processing, Post-Transcriptional; RNA-Binding Proteins
PubMed: 36067707
DOI: 10.1016/j.sbi.2022.102442