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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 -
International Journal of Molecular... Mar 2020Altered gene expression is the primary molecular mechanism responsible for the pathological processes of human diseases, including cancer. MicroRNAs (miRNAs) are... (Review)
Review
Altered gene expression is the primary molecular mechanism responsible for the pathological processes of human diseases, including cancer. MicroRNAs (miRNAs) are virtually involved at the post-transcriptional level and bind to 3' UTR of their target messenger RNA (mRNA) to suppress expression. Dysfunction of miRNAs disturbs expression of oncogenic or tumor-suppressive target genes, which is implicated in cancer pathogenesis. As such, a large number of miRNAs have been found to be downregulated or upregulated in human cancers and to function as oncomiRs or oncosuppressor miRs. Notably, the molecular mechanism underlying the dysregulation of miRNA expression in cancer has been recently uncovered. The genetic deletion or amplification and epigenetic methylation of miRNA genomic loci and the transcription factor-mediated regulation of primary miRNA often alter the landscape of miRNA expression in cancer. Dysregulation of the multiple processing steps in mature miRNA biogenesis can also cause alterations in miRNA expression in cancer. Detailed knowledge of the regulatory mechanism of miRNAs in cancer is essential for understanding its physiological role and the implications of cancer-associated dysfunction and dysregulation. In this review, we elucidate how miRNA expression is deregulated in cancer, paying particular attention to the cancer-associated transcriptional and post-transcriptional factors that execute miRNA programs.
Topics: Animals; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Neoplasms; RNA, Messenger
PubMed: 32138313
DOI: 10.3390/ijms21051723 -
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 -
International Journal of Molecular... Dec 2019MicroRNAs (miRNAs) are small non-coding RNAs with the capability of modulating gene expression at the post-transcriptional level either by inhibiting messenger RNA... (Review)
Review
MicroRNAs (miRNAs) are small non-coding RNAs with the capability of modulating gene expression at the post-transcriptional level either by inhibiting messenger RNA (mRNA) translation or by promoting mRNA degradation. The outcome of a myriad of physiological processes and pathologies, including cancer, cardiovascular and metabolic diseases, relies highly on miRNAs. However, deciphering the precise roles of specific miRNAs in these pathophysiological contexts is challenging due to the high levels of complexity of their actions. Indeed, regulation of mRNA expression by miRNAs is frequently cell/organ specific; highly dependent on the stress and metabolic status of the organism; and often poorly correlated with miRNA expression levels. Such biological features of miRNAs suggest that various regulatory mechanisms control not only their expression, but also their activity and/or bioavailability. Several mechanisms have been described to modulate miRNA action, including genetic polymorphisms, methylation of miRNA promoters, asymmetric miRNA strand selection, interactions with RNA-binding proteins (RBPs) or other coding/non-coding RNAs. Moreover, nucleotide modifications (A-to-I or C-to-U) within the miRNA sequences at different stages of their maturation are also critical for their functionality. This regulatory mechanism called "RNA editing" involves specific enzymes of the adenosine/cytidine deaminase family, which trigger single nucleotide changes in primary miRNAs. These nucleotide modifications greatly influence a miRNA's stability, maturation and activity by changing its specificity towards target mRNAs. Understanding how editing events impact miRNA's ability to regulate stress responses in cells and organs, or the development of specific pathologies, e.g., metabolic diseases or cancer, should not only deepen our knowledge of molecular mechanisms underlying complex diseases, but can also facilitate the design of new therapeutic approaches based on miRNA targeting. Herein, we will discuss the current knowledge on miRNA editing and how this mechanism regulates miRNA biogenesis and activity.
Topics: Animals; Gene Expression Regulation; Humans; MicroRNAs; Neoplasms; RNA Editing
PubMed: 31835747
DOI: 10.3390/ijms20246249 -
International Journal of Medical... 2022Circular RNA (circRNA) is a novel endogenous non-coding RNA (ncRNA) that, like microRNA (miRNA), is a rapidly emerging RNA research topic. CircRNA, unlike traditional... (Review)
Review
Circular RNA (circRNA) is a novel endogenous non-coding RNA (ncRNA) that, like microRNA (miRNA), is a rapidly emerging RNA research topic. CircRNA, unlike traditional linear RNAs (which have 5' and 3' ends), has a closed-loop structure that is unaffected by RNA exonucleases. Thus, circRNA has sustained expression and is less sensitive to degradation. Since circRNAs have many miRNAs binding sites, eliminating their repressive effects on their target genes can strongly enhance their expression. CircRNAs serve an important regulatory role in disease onset and progression via specific circRNA-miRNA interactions. We summarized the current progress in elucidating mechanisms and biogenesis of circRNAs in this review. In particular, circRNAs can function mainly as miRNA sponges, regulating host gene expression and protein transportation. Finally, we discussed the application prospects and significant challenges for the development of circRNA-based therapeutics.
Topics: Binding Sites; MicroRNAs; RNA; RNA, Circular
PubMed: 35813288
DOI: 10.7150/ijms.71840 -
Cell May 2022Cancer cells are featured with uncontrollable activation of cell cycle, and microRNA deficiency drives tumorigenesis. The RNA-dependent RNA polymerase (RDR) is essential...
Cancer cells are featured with uncontrollable activation of cell cycle, and microRNA deficiency drives tumorigenesis. The RNA-dependent RNA polymerase (RDR) is essential for small-RNA-mediated immune response in plants but is absent in vertebrates. Here, we show that ectopic expression of plant RDR1 can generally inhibit cancer cell proliferation. In many human primary tumors, abnormal microRNA isoforms with 1-nt-shorter 3' ends are widely accumulated. RDR1 with nucleotidyltransferase activity can recognize and modify the problematic AGO2-free microRNA duplexes with mononucleotides to restore their 2 nt overhang structure, which eventually rescues AGO2-loading efficiency and elevates global miRNA expression to inhibit cancer cell-cycle specifically. The broad antitumor effects of RDR1, which can be delivered by an adeno-associated virus, are visualized in multiple xenograft tumor models in vivo. Altogether, we reveal the widespread accumulation of aberrant microRNA isoforms in tumors and develop a plant RDR1-mediated antitumor stratagem by editing and repairing defective microRNAs.
Topics: Animals; Humans; Immunity; MicroRNAs; Plant Proteins; Plants; RNA-Dependent RNA Polymerase
PubMed: 35623329
DOI: 10.1016/j.cell.2022.04.030 -
Cells Nov 2022Firstly, I apologize for the delayed publication of this Special Issue in the form of a book title [...].
Firstly, I apologize for the delayed publication of this Special Issue in the form of a book title [...].
Topics: Computational Biology; MicroRNAs
PubMed: 36429104
DOI: 10.3390/cells11223677 -
Bone Sep 2021MicroRNAs, identified in the early 1990s, are believed to regulate approximately 30% of the human genome. The role of microRNA in bone cells was first reported in 2007... (Review)
Review
MicroRNAs, identified in the early 1990s, are believed to regulate approximately 30% of the human genome. The role of microRNA in bone cells was first reported in 2007 in a manuscript showing that microRNA-223 is essential for osteoclast differentiation in vitro, and a few studies reported a role of microRNAs in osteoblasts the same year. The first report of microRNA actions in osteocytes was published in 2010, in which it was demonstrated that the microRNA cluster 23a~27a~24-2 regulates osteocyte differentiation. Since then, few studies have described the role of these 18-25-nucleotide non-coding RNAs on osteocyte biology, reporting osteocytes both as producers and as targets of the actions of microRNAs. We review here the current knowledge on the effects of microRNAs on osteocyte biology.
Topics: Cell Differentiation; Humans; MicroRNAs; Osteoblasts; Osteocytes
PubMed: 33965651
DOI: 10.1016/j.bone.2021.115994 -
International Journal of Molecular... Jul 2022Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), which represent the range of dystrophinopathies, account for nearly 80% of muscle dystrophy. DMD... (Review)
Review
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), which represent the range of dystrophinopathies, account for nearly 80% of muscle dystrophy. DMD and BMD result from the loss of a functional dystrophin protein, and the leading cause of death in these patients is cardiac remodeling and heart failure. The pathogenesis and progression of the more severe form of DMD have been extensively studied and are controlled by many determinants, including microRNAs (miRNAs). The regulatory role of miRNAs in muscle function and the differential miRNA expression in muscular dystrophy indicate the clinical significance of miRNAs. This review discusses the relevant microRNAs as potential biomarkers and therapeutic targets for DMD and DMD cardiomyopathy as examples of dystrophinopathies.
Topics: Biomarkers; Cardiomyopathies; Dystrophin; Heart; Humans; MicroRNAs; Muscular Dystrophy, Duchenne
PubMed: 35887128
DOI: 10.3390/ijms23147785 -
International Journal of Molecular... Apr 2022Circulating microRNAs (c-microRNAs, c-miRNAs), which are present in almost all biological fluids, are promising sensitive biomarkers for various diseases (oncological... (Review)
Review
Circulating microRNAs (c-microRNAs, c-miRNAs), which are present in almost all biological fluids, are promising sensitive biomarkers for various diseases (oncological and cardiovascular diseases, neurodegenerative pathologies, etc.), and their signatures accurately reflect the state of the body. Studies of the expression of microRNA markers show that they can enable a wide range of diseases to be diagnosed before clinical symptoms are manifested, and they can help to assess a patient's response to therapy in order to correct and personalize treatments. This review discusses the latest trends in the uses of miRNAs for diagnosing and treating various diseases, viral and non-viral. It is concluded that exogenous microRNAs can be used as high-precision therapeutic agents for these purposes.
Topics: Biomarkers; Cardiovascular Diseases; Circulating MicroRNA; Humans; Medicine; MicroRNAs
PubMed: 35409354
DOI: 10.3390/ijms23073996