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BMB Reports Jun 2016Innate immune responses are primary, relatively limited, and specific responses to numerous pathogens and toxic molecules. Protein expression involved in these innate... (Review)
Review
Innate immune responses are primary, relatively limited, and specific responses to numerous pathogens and toxic molecules. Protein expression involved in these innate responses must be tightly regulated at both transcriptional level and post-transcriptional level to avoid the development of excessive inflammation that can be potentially harmful to the host. MicroRNAs are small noncoding RNAs (~22 nucleotides [nts]) that participate in the regulation of numerous physiological responses by targeting specific messenger RNAs to suppress their translation. Recent work has shown that several negative regulators of transcription including microRNAs play important roles in inhibiting the exacerbation of inflammatory responses and in the maintenance of immunological homeostasis. This emerging research area will provide new insights on how microRNAs regulate innate immune signaling. It might show that dysregulation of microRNA synthesis is associated with the pathogenesis of inflammatory and infectious diseases. In this review, we focused on miR-146 and miR-125 and described the roles these miRNAs in modulating innate immune signaling. These microRNAs can control inflammatory responses and the outcomes of pathogenic infections. [BMB Reports 2016; 49(6): 311-318].
Topics: Animals; Gene Expression Regulation; Humans; Immunity, Innate; Inflammation; MicroRNAs; Signal Transduction; Toll-Like Receptors
PubMed: 26996343
DOI: 10.5483/bmbrep.2016.49.6.056 -
Frontiers in Bioscience (Scholar... Jun 2022Obesity and osteoporosis are global health problems characterized by high rates of prevalence and mortality due to complications. As people with visceral obesity age,... (Review)
Review
Obesity and osteoporosis are global health problems characterized by high rates of prevalence and mortality due to complications. As people with visceral obesity age, the adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) increases, and adipocytes become the predominant stromal cells in the bone marrow microenvironment, which hinders the physiological regeneration and mineralization of bone tissue. Primary and secondary osteoporosis remain severe progressive diseases. Both osteoporosis and obesity are associated with microRNAs (miRNAs) that induce adipogenesis and osteoresorption. This review presents analyses of the roles and clinical potential of miRNAs in the epigenetic control of BMSC differentiation and the formation and function of osteoclasts in osteoporosis with and without obesity. Understanding the fine-tuned regulation of the expression of genes critical for the balance of osteogenesis/osteolysis processes may provide hope for the development of effective and safe osteoporosis therapies in the future.
Topics: Cell Differentiation; Humans; Mesenchymal Stem Cells; MicroRNAs; Obesity; Osteogenesis; Osteoporosis
PubMed: 36137980
DOI: 10.31083/j.fbs1403017 -
Clinical Chemistry and Laboratory... May 2017Circulating blood platelets play a central role in the maintenance of hemostasis. They adhere to subendothelial extracellular matrix proteins that become exposed upon... (Review)
Review
Circulating blood platelets play a central role in the maintenance of hemostasis. They adhere to subendothelial extracellular matrix proteins that become exposed upon vessel wall damage, which is followed by platelet activation, further platelet recruitment, platelet aggregation and formation of an occlusive, or non-occlusive, platelet thrombus. Platelets host a surprisingly diverse transcriptome, which is comprised of ~9500 messenger RNAs (mRNAs) and different classes of non-coding RNAs, including microRNAs, as well as a significant repertoire of proteins that contribute to their primary (adhesion, aggregation, granule secretion) and alternative (RNA transfer, mRNA translation, immune regulation) functions. Platelets have the propensity to release microparticles (MPs; 0.1-1 μm in diameter) upon activation, which may mediate inflammatory responses and contribute to exacerbate inflammatory diseases and conditions. Carrying components of the platelets' cytoplasm, platelet MPs may exert their effects on recipient cells by transferring their content in platelet-derived bioactive lipid mediators, cytokines, mRNAs and microRNAs. Platelet MP-associated microRNAs may thus function also outside of platelets and play an important role in intercellular signaling and gene expression programming across the entire circulatory system. The role and importance of platelet MP-associated microRNAs in various aspects of biology and pathophysiology are increasingly recognized, and now provide the scientific basis and rationale to support further translational research and clinical studies. The clinical significance, pathophysiological role as well as the diagnostic and therapeutic potential of platelet MP-associated microRNAs in cardiovascular diseases, platelet transfusion and cancer will be discussed.
Topics: Blood Platelets; Cell-Derived Microparticles; Exosomes; Humans; MicroRNAs; Platelet Activation
PubMed: 28099120
DOI: 10.1515/cclm-2016-0895 -
International Journal of Molecular... Dec 2019MicroRNAs (miRNAs) are approximately 22-nucleotide-long, small non-coding RNAs that post-transcriptionally regulate gene expression. The biogenesis of miRNAs involves... (Review)
Review
MicroRNAs (miRNAs) are approximately 22-nucleotide-long, small non-coding RNAs that post-transcriptionally regulate gene expression. The biogenesis of miRNAs involves multiple steps, including the transcription of primary miRNAs (pri-miRNAs), nuclear Drosha-mediated processing, cytoplasmic Dicer-mediated processing, and loading onto Argonaute (Ago) proteins. Further, miRNAs control diverse biological and pathological processes via the silencing of target mRNAs. This review summarizes recent findings regarding the quantitative aspects of miRNA homeostasis, including Drosha-mediated pri-miRNA processing, Ago-mediated asymmetric miRNA strand selection, and modifications of miRNA pathway components, as well as the roles of RNA modifications (epitranscriptomics), epigenetics, transcription factor circuits, and super-enhancers in miRNA regulation. These recent advances have facilitated a system-level understanding of miRNA networks, as well as the improvement of RNAi performance for both gene-specific targeting and genome-wide screening. The comprehensive understanding and modeling of miRNA biogenesis and function have been applied to the design of synthetic gene circuits. In addition, the relationships between miRNA genes and super-enhancers provide the molecular basis for the highly biased cell type-specific expression patterns of miRNAs and the evolution of miRNA-target connections, while highlighting the importance of alterations of super-enhancer-associated miRNAs in a variety of human diseases.
Topics: Animals; Argonaute Proteins; Humans; MicroRNAs; RNA, Messenger; Synthetic Biology
PubMed: 31878193
DOI: 10.3390/ijms21010132 -
Biomedicine & Pharmacotherapy =... Sep 2023MicroRNAs (miRNAs) are a class of small non-coding RNAs that post-transcriptionally regulate the expression of approximately 50 % of all protein-coding genes. They have... (Review)
Review
MicroRNAs (miRNAs) are a class of small non-coding RNAs that post-transcriptionally regulate the expression of approximately 50 % of all protein-coding genes. They have been demonstrated to act as key regulators in various pathophysiological processes and play significant roles in a wide range of human diseases, particularly cancer. Current research highlights the aberrant expression of microRNA-488 (miR-488) in multiple human diseases and its critical involvement in disease initiation and progression. Moreover, the expression level of miR-488 has been linked to clinicopathological features and patient prognosis across different diseases. However, a comprehensive systematic review of miR-488 is lacking. Therefore, our study aims to consolidate the current knowledge surrounding miR-488, with a primary focus on its emerging biological functions, regulatory mechanisms, and potential clinical applications in human diseases. Through this review, we aim to establish a comprehensive understanding of the diverse roles of miR-488 in the development of various diseases.
Topics: Humans; MicroRNAs; Neoplasms
PubMed: 37418982
DOI: 10.1016/j.biopha.2023.115115 -
Advanced Science (Weinheim,... Nov 2023Liver metastasis is a common cause of death in progressive colorectal cancer patients, but the molecular mechanisms remain unclear. Here, it is reported that a conserved...
CircNOLC1 Promotes Colorectal Cancer Liver Metastasis by Interacting with AZGP1 and Sponging miR-212-5p to Regulate Reprogramming of the Oxidative Pentose Phosphate Pathway.
Liver metastasis is a common cause of death in progressive colorectal cancer patients, but the molecular mechanisms remain unclear. Here, it is reported that a conserved and oxidative pentose phosphate pathway-associated circular RNA, circNOLC1, plays a crucial role in colorectal cancer liver metastasis. It is found that circNOLC1 silencing reduces the oxidative pentose phosphate pathway-related intermediate metabolites and elevates NADP /NADPH ratio and intracellular ROS levels, thereby attenuating colorectal cancer cell proliferation, migration, and liver metastasis. circNOLC1 interacting with AZGP1 to activate mTOR/SREBP1 signaling, or sponging miR-212-5p to upregulate c-Met expression, both of which can further induce G6PD to activate oxidative pentose phosphate pathway in colorectal cancer liver metastasis. Moreover, circNOLC1 is regulated by the transcription factor YY1 and specifically stabilized HuR induces its parental gene mRNA expression. The associations between circNOLC1 and these signaling molecules are validated in primary CRC and corresponding liver metastasis tissues. These findings reveal that circNOLC1 interacting with AZGP1 and circNOLC1/miR-212-5p/c-Met axis plays a key role in oxidative pentose phosphate pathway-mediated colorectal cancer liver metastasis, which may provide a novel target for precision medicine of colorectal cancer.
Topics: Humans; MicroRNAs; Colorectal Neoplasms; Pentose Phosphate Pathway; Liver Neoplasms; Oxidative Stress; Adipokines
PubMed: 37870214
DOI: 10.1002/advs.202205229 -
RNA (New York, N.Y.) Jan 2020Within the forensic science community, there is a continued push to develop novel tools to aid in criminal investigations. microRNA (miRNA) analysis has been the focus... (Review)
Review
Within the forensic science community, there is a continued push to develop novel tools to aid in criminal investigations. microRNA (miRNA) analysis has been the focus of many researcher's attention in the biomedical field since its discovery in 1993; however, the forensic application of miRNA analysis has only been suggested within the last 10 years and has been gaining considerable traction recently. The primary focus of the forensic application of miRNA analysis has been on body fluid identification to provide confirmatory universal analysis of unknown biological stains obtained from crime scenes or evidence items. There are, however, other forensic applications of miRNA profiling that have shown potential, yet are largely understudied, and warrant further investigation such as organ tissue identification, donor age estimation, and more. This review paper aims to evaluate the current literature and future potential of miRNA analysis within the forensic science field.
Topics: Forensic Anthropology; Forensic Medicine; Forensic Sciences; Humans; MicroRNAs
PubMed: 31658993
DOI: 10.1261/rna.072173.119 -
Proceedings of the National Academy of... Oct 2023The nuclear cleavage of a suboptimal primary miRNA hairpin by the Drosha/DGCR8 complex ("Microprocessor") can be enhanced by an optimal miRNA neighbor, a phenomenon...
The nuclear cleavage of a suboptimal primary miRNA hairpin by the Drosha/DGCR8 complex ("Microprocessor") can be enhanced by an optimal miRNA neighbor, a phenomenon termed cluster assistance. Several features and biological impacts of this new layer of miRNA regulation are not fully known. Here, we elucidate the parameters of cluster assistance of a suboptimal miRNA and also reveal competitive interactions amongst optimal miRNAs within a cluster. We exploit cluster assistance as a functional assay for suboptimal processing and use this to invalidate putative suboptimal substrates, as well as identify a "solo" suboptimal miRNA. Finally, we report complexity in how specific mutations might affect the biogenesis of clustered miRNAs in disease contexts. This includes how an operon context can buffer the effect of a deleterious processing variant, but reciprocally how a point mutation can have a nonautonomous effect to impair the biogenesis of a clustered, suboptimal, neighbor. These data expand our knowledge regarding regulated miRNA biogenesis in humans and represent a functional assay for empirical definition of suboptimal Microprocessor substrates.
Topics: Humans; MicroRNAs; RNA Processing, Post-Transcriptional; RNA-Binding Proteins; Ribonuclease III
PubMed: 37788316
DOI: 10.1073/pnas.2306727120 -
BMC Immunology Feb 2023A comprehensive dissection of the role of microRNAs (miRNAs) in gene regulation and subsequent cell functions requires a specific and efficient knockdown or...
BACKGROUND
A comprehensive dissection of the role of microRNAs (miRNAs) in gene regulation and subsequent cell functions requires a specific and efficient knockdown or overexpression of the miRNA of interest; these are achieved by transfecting the cell of interest with a miRNA inhibitor or a miRNA mimic, respectively. Inhibitors and mimics of miRNAs with a unique chemistry and/or structural modifications are available commercially and require different transfection conditions. Here, we aimed to investigate how various conditions affect the transfection efficacy of two miRNAs with high and low endogenous expression, miR-15a-5p and miR-20b-5p respectively, in human primary cells.
RESULTS
MiRNA inhibitors and mimics from two commonly used commercial vendors were employed, i.e., mirVana (Thermo Fisher Scientific) and locked nucleic acid (LNA) miRNA (Qiagen). We systematically examined and optimized the transfection conditions of such miRNA inhibitors and mimics to primary endothelial cells and monocytes using either a lipid-based carrier (lipofectamine) for delivery or an unassisted uptake. Transfection of LNA inhibitors with either phosphodiester (PE)- or phosphorothioate (PS)-modified nucleotide bonds, delivered using a lipid-based carrier, efficiently downregulated the expression levels of miR-15a-5p already 24 h following transfection. MirVana miR-15a-5p inhibitor displayed a less efficient inhibitory effect, which was not improved 48 h following a single transfection or two consecutive transfections. Interestingly, LNA-PS miR-15a-5p inhibitor efficiently reduced the levels of miR-15a-5p when delivered without a lipid-based carrier in both ECs and monocytes. When using a carrier, mirVana and LNA miR-15a-5p and miR-20b-5p mimics showed similar efficiency 48 h following transfection to ECs and monocytes. None of the miRNA mimics effectively induced overexpression of the respective miRNA when given to primary cells without a carrier.
CONCLUSION
LNA miRNA inhibitors efficiently downregulated the cellular expression of miRNA, such as miR-15a-5p. Furthermore, our findings suggest that LNA-PS miRNA inhibitors can be delivered in the absence of a lipid-based carrier, whereas miRNA mimics need the aid of a lipid-based carrier to achieve sufficient cellular uptake.
Topics: Humans; Endothelial Cells; Workflow; MicroRNAs; Gene Expression Regulation
PubMed: 36792999
DOI: 10.1186/s12865-023-00540-9 -
Fertility and Sterility Jun 2014MicroRNAs, also called miRNAs, are small 19-22 nucleotide (nt) sequences of noncoding RNA that work as endogenous epigenetic gene expression regulators. They are... (Review)
Review
MicroRNAs, also called miRNAs, are small 19-22 nucleotide (nt) sequences of noncoding RNA that work as endogenous epigenetic gene expression regulators. They are transcribed as large primary miRNAs or pre-miRNAs by RNA polymerase II and III, and are subsequently processed by the ribonucleases Drosha and Dicer to give rise to their mature forms. These mature miRNAs are then incorporated into the RISC complex (RNA-induced silencing complex) where they bind to the 3'-UTR mRNA complementary region, which induces their degradation or inhibits their translation, resulting in gene silencing. MicroRNAs are essential for embryo, cell, and tissue development, regulating cell differentiation, proliferation, and apoptosis, hence their importance in human reproduction. Currently, methods of detecting these molecules include real-time polymerase chain reaction, microarrays, in situ hybridization, and deep sequencing as well as novel approaches such as Nanostring nCounter. However, functional characterization is still required to confirm their biologic roles. Furthermore, miRNAs are not only found in cells but also have been identified in most biologic fluids, including serum, plasma, and saliva. Once miRNAs are secreted by cells, they are either incorporated into microvesicles or become associated with proteins, which protect them from RNase degradation so that they may remain intact for long periods of time. This suggests that they might also mediate paracrine signaling via different pathways and could therefore represent potential new biomarkers. Indeed, many pharmaceutic companies have recently started to investigate these molecules as possible routes to develop new human disease treatments.
Topics: Animals; Gene Expression Regulation; Genetic Markers; Genetic Therapy; Humans; MicroRNAs; Signal Transduction; Terminology as Topic
PubMed: 24314918
DOI: 10.1016/j.fertnstert.2013.10.042