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International Journal of Molecular... Jun 2022MicroRNAs (miRNAs) are a group of endogenous non-coding RNAs that regulate gene expression. Alteration in miRNA expression results in changes in the profile of genes... (Review)
Review
MicroRNAs (miRNAs) are a group of endogenous non-coding RNAs that regulate gene expression. Alteration in miRNA expression results in changes in the profile of genes involving a range of biological processes, contributing to numerous human disorders. With high stability in human fluids, miRNAs in the circulation are considered as promising biomarkers for diagnosis, as well as prognosis of disease. In addition, the translation of miRNA-based therapy from a research setting to clinical application has huge potential. The aim of the current review is to: (i) discuss how miRNAs traffic intracellularly and extracellularly; (ii) emphasize the role of circulating miRNAs as attractive potential biomarkers for diagnosis and prognosis; (iii) describe how circulating microRNA can be measured, emphasizing technical problems that may influence their relative levels; (iv) highlight some of the circulating miRNA panels available for clinical use; (v) discuss how miRNAs could be utilized as novel therapeutics, and finally (v) update those miRNA-based therapeutics clinical trials that could potentially lead to a breakthrough in the treatment of different human pathologies.
Topics: Biomarkers; Circulating MicroRNA; Humans; MicroRNAs
PubMed: 35806173
DOI: 10.3390/ijms23137167 -
The Journal of Allergy and Clinical... Apr 2018MicroRNAs (miRNAs) are small endogenous RNAs that regulate gene-expression posttranscriptionally. MiRNA research in allergy is expanding because miRNAs are crucial... (Review)
Review
MicroRNAs (miRNAs) are small endogenous RNAs that regulate gene-expression posttranscriptionally. MiRNA research in allergy is expanding because miRNAs are crucial regulators of gene expression and promising candidates for biomarker development. MiRNA mimics and miRNA inhibitors currently in preclinical development have shown promise as novel therapeutic agents. Multiple technological platforms have been developed for miRNA isolation, miRNA quantitation, miRNA profiling, miRNA target detection, and modulating miRNA levels in vitro and in vivo. Here we will review the major technological platforms with consideration given for the advantages and disadvantages of each platform.
Topics: Gene Expression Regulation; Genetic Markers; Humans; Hypersensitivity; In Vitro Techniques; MicroRNAs
PubMed: 29074454
DOI: 10.1016/j.jaci.2017.08.034 -
Seminars in Liver Disease Feb 2015In considering an overview of microRNA biology, it is useful to consider microRNAs as a part of cellular communication. At the simplest level, microRNAs act to decrease... (Review)
Review
In considering an overview of microRNA biology, it is useful to consider microRNAs as a part of cellular communication. At the simplest level, microRNAs act to decrease the expression of messenger RNAs that contain stretches of sequence complementary to the microRNA. This function can be likened to the function of endogenous or synthetic short interfering RNA. However, microRNA function is more complicated and nuanced than this "on-off" model would suggest. Further, many microRNA targets are themselves noncoding RNAs. In this review, the authors discuss the role of microRNAs in shaping the proteome of the cell in a way that is consistent with microRNA involvement in a highly regulated conversation, sensitive to outside influence and internal feedback.
Topics: Alternative Splicing; Gene Expression Regulation; Genetic Markers; Humans; MicroRNAs; Polymorphism, Single Nucleotide; RNA Processing, Post-Transcriptional; Ribonucleoproteins
PubMed: 25632930
DOI: 10.1055/s-0034-1397344 -
Nature Reviews. Genetics Apr 2012MicroRNAs (miRNAs) are small RNAs that post-transcriptionally regulate the expression of thousands of genes in a broad range of organisms in both normal physiological... (Review)
Review
MicroRNAs (miRNAs) are small RNAs that post-transcriptionally regulate the expression of thousands of genes in a broad range of organisms in both normal physiological contexts and in disease contexts. miRNA expression profiling is gaining popularity because miRNAs, as key regulators in gene expression networks, can influence many biological processes and also show promise as biomarkers for disease. Technological advances have spawned a multitude of platforms for miRNA profiling, and an understanding of the strengths and pitfalls of different approaches can aid in their effective use. Here, we review the major considerations for carrying out and interpreting results of miRNA-profiling studies.
Topics: Animals; Base Sequence; Databases, Genetic; Gene Expression Profiling; Gene Expression Regulation; High-Throughput Nucleotide Sequencing; MicroRNAs; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, RNA
PubMed: 22510765
DOI: 10.1038/nrg3198 -
Trends in Genetics : TIG Jun 2022MicroRNAs (miRNAs) are very powerful genetic regulators, as evidenced by the fact that a single miRNA can direct entire cellular pathways via interacting with a broad... (Review)
Review
MicroRNAs (miRNAs) are very powerful genetic regulators, as evidenced by the fact that a single miRNA can direct entire cellular pathways via interacting with a broad spectrum of target genes. This property renders miRNAs as highly interesting therapeutic tools to restore cell functions that are altered as part of a disease phenotype. However, this strength of miRNAs is also a weakness because their cellular effects are so numerous that off-target effects can hardly be avoided. In this review, we point out the main challenges and the strategies to specifically address the problems that need to be surmounted in the push toward a therapeutic application of miRNAs. Particular emphasis is given to approaches that have already found their way into clinical studies.
Topics: Humans; MicroRNAs; Neoplasms
PubMed: 35303998
DOI: 10.1016/j.tig.2022.02.006 -
Nucleic Acids Research Jan 2006The miRBase database aims to provide integrated interfaces to comprehensive microRNA sequence data, annotation and predicted gene targets. miRBase takes over...
The miRBase database aims to provide integrated interfaces to comprehensive microRNA sequence data, annotation and predicted gene targets. miRBase takes over functionality from the microRNA Registry and fulfils three main roles: the miRBase Registry acts as an independent arbiter of microRNA gene nomenclature, assigning names prior to publication of novel miRNA sequences. miRBase Sequences is the primary online repository for miRNA sequence data and annotation. miRBase Targets is a comprehensive new database of predicted miRNA target genes. miRBase is available at http://microrna.sanger.ac.uk/.
Topics: Animals; Base Sequence; Databases, Nucleic Acid; Gene Expression Regulation; Internet; MicroRNAs; Registries; Terminology as Topic; User-Computer Interface
PubMed: 16381832
DOI: 10.1093/nar/gkj112 -
Cell Reports Dec 2013Short hairpin RNA (shRNA) technology enables stable and regulated gene repression. For establishing experimentally versatile RNAi tools and minimizing toxicities,...
Short hairpin RNA (shRNA) technology enables stable and regulated gene repression. For establishing experimentally versatile RNAi tools and minimizing toxicities, synthetic shRNAs can be embedded into endogenous microRNA contexts. However, due to our incomplete understanding of microRNA biogenesis, such "shRNAmirs" often fail to trigger potent knockdown, especially when expressed from a single genomic copy. Following recent advances in design of synthetic shRNAmir stems, here we take a systematic approach to optimize the experimental miR-30 backbone. Among several favorable features, we identify a conserved element 3' of the basal stem as critically required for optimal shRNAmir processing and implement it in an optimized backbone termed "miR-E", which strongly increases mature shRNA levels and knockdown efficacy. Existing miR-30 reagents can be easily converted to miR-E, and its combination with up-to-date design rules establishes a validated and accessible platform for generating effective single-copy shRNA libraries that will facilitate the functional annotation of the genome.
Topics: Cell Line, Tumor; Gene Knockdown Techniques; Humans; MicroRNAs; Nucleotide Motifs
PubMed: 24332856
DOI: 10.1016/j.celrep.2013.11.020 -
Journal of Experimental & Clinical... Feb 2019MicroRNA-34 (miR-34) has been reported to be dysregulated in various human cancers and regarded as a tumor suppressive microRNA because of its synergistic effect with... (Review)
Review
MicroRNA-34 (miR-34) has been reported to be dysregulated in various human cancers and regarded as a tumor suppressive microRNA because of its synergistic effect with the well-known tumor suppressor p53. Along with the application of MRX34, the first tumor-targeted microRNA drug which based on miR-34a mimics, on phase I clinical trial (NCT01829971), the significance of miR-34 is increasingly recognized. miR-34 plays a crucial role on repressing tumor progression by involving in epithelial-mesenchymal transition (EMT) via EMT- transcription factors, p53 and some important signal pathways. Not only that, numerous preclinical researches revealed the giant potential of miR-34a on cancer therapy through diversiform nano-scaled delivery systems. Here, we provide an overview about the function of miR-34 in various cancers and the mechanism of miR-34 in tumor-associated EMT. Furthermore, its potential role as a microRNA therapeutic candidate is also discussed. Notwithstanding some obstacles existed, the extensive application prospect of miR-34 on oncotherapy cannot be neglected.
Topics: Animals; Drug Delivery Systems; Epithelial-Mesenchymal Transition; Genes, Tumor Suppressor; Humans; Mice; MicroRNAs; Molecular Mimicry; Nanoparticles; Neoplasms; Signal Transduction; Transcription Factors; Tumor Suppressor Protein p53
PubMed: 30717802
DOI: 10.1186/s13046-019-1059-5 -
Veterinary Pathology Jul 2014The discovery of microRNAs (miRNAs) in 1993 followed by developments and discoveries in small RNA biology have redefined the biological landscape by significantly... (Review)
Review
The discovery of microRNAs (miRNAs) in 1993 followed by developments and discoveries in small RNA biology have redefined the biological landscape by significantly altering the longstanding dogmas that defined gene regulation. These small RNAs play a significant role in modulation of an array of physiological and pathological processes ranging from embryonic development to neoplastic progression. Unique miRNA signatures of various inherited, metabolic, infectious, and neoplastic diseases have added a new dimension to the studies that look at their pathogenesis and highlight their potential to be reliable biomarkers. Also, altering miRNA functionality and the development of novel in vivo delivery systems to achieve targeted modulation of specific miRNA function are being actively pursued as novel approaches for therapeutic intervention in many diseases. Here we review the current body of knowledge on the role of miRNAs in development and disease and discuss future implications.
Topics: Animal Diseases; Animals; Biomarkers; Growth and Development; History, 20th Century; History, 21st Century; MicroRNAs; Models, Biological
PubMed: 24045890
DOI: 10.1177/0300985813502820 -
The New Phytologist Feb 20171030 I. 1030 II. 1030 III. 1031 IV. 1031 V. 1032 VI. 1033 VII. 1034 VIII. 1034 1034 References 1034 SUMMARY: Copper (Cu) microRNAs are upregulated by Cu deficiency and... (Review)
Review
1030 I. 1030 II. 1030 III. 1031 IV. 1031 V. 1032 VI. 1033 VII. 1034 VIII. 1034 1034 References 1034 SUMMARY: Copper (Cu) microRNAs are upregulated by Cu deficiency and mediate the post-transcriptional downregulation of transcripts that encode Cu proteins, suggesting a role directly related to Cu. However, expression and phenotypic analyses of copper microRNA mutants and over-expressors have suggested roles mainly in tolerance to abiotic stresses. To reconcile available data, a model is proposed which emphasizes the mobile nature of copper microRNA molecules in the regulation of Cu homeostasis. It is proposed that the Cu-microRNA regulatory circuits are further co-opted by plants to regulate both beneficial and pathogenic interactions with microbes. Further exploration of Cu-microRNA functions that account for the cell-to-cell mobility should give novel insight into plant microbe interactions and the integration of micronutrition and development.
Topics: Conserved Sequence; Copper; Gene Expression Regulation, Plant; Homeostasis; MicroRNAs; Plants
PubMed: 27767213
DOI: 10.1111/nph.14244