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      The current landscape of microRNAs (miRNAs) in bacterial pneumonia: opportunities and challenges

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          Abstract

          MicroRNAs (miRNAs), which were initially discovered in Caenorhabditis elegans, can regulate gene expression by recognizing cognate sequences and interfering with the transcriptional or translational machinery. The application of bioinformatics tools for structural analysis and target prediction has largely driven the investigation of certain miRNAs. Notably, it has been found that certain miRNAs which are widely involved in the inflammatory response and immune regulation are closely associated with the occurrence, development, and outcome of bacterial pneumonia. It has been shown that certain miRNA techniques can be used to identify related targets and explore associated signal transduction pathways. This enhances the understanding of bacterial pneumonia, notably for “refractory” or drug-resistant bacterial pneumonia. Although these miRNA-based methods may provide a basis for the clinical diagnosis and treatment of this disease, they still face various challenges, such as low sensitivity, poor specificity, low silencing efficiency, off-target effects, and toxic reactions. The opportunities and challenges of these methods have been completely reviewed, notably in bacterial pneumonia. With the continuous improvement of the current technology, the miRNA-based methods may surmount the aforementioned limitations, providing promising support for the clinical diagnosis and treatment of “refractory” or drug-resistant bacterial pneumonia.

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          MicroRNA

          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.
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            Regulation of microRNA function in animals

            Since their serendipitous discovery in nematodes, microRNAs (miRNAs) have emerged as key regulators of biological processes in animals. These small RNAs form complex regulatory networks in cell development, differentiation and homeostasis. Deregulation of miRNA function is associated with an increasing number of human diseases, particularly cancer. Recent discoveries have expanded our understanding of how miRNAs are regulated. Here we review the mechanisms that modulate miRNA activity, their stability and their localization through alternative processing, sequence editing, post-translational modifications of Argonaute proteins, viral factors, transport from the cytoplasm and regulation of miRNA–target interactions. We conclude by discussing intriguing open questions to be answered by future research.
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              The current state and future directions of RNAi-based therapeutics

              The RNA interference (RNAi) pathway regulates mRNA stability and translation in nearly all human cells. Small double-stranded RNA molecules can efficiently trigger RNAi silencing of specific genes, but their therapeutic use has faced numerous challenges involving safety and potency. However, August 2018 marked a new era for the field, with the US Food and Drug Administration approving patisiran, the first RNAi-based drug. In this Review, we discuss key advances in the design and development of RNAi drugs leading up to this landmark achievement, the state of the current clinical pipeline and prospects for future advances, including novel RNAi pathway agents utilizing mechanisms beyond post-translational RNAi silencing.
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                Author and article information

                Contributors
                18211197728@163.com
                Journal
                Cell Mol Biol Lett
                Cell Mol Biol Lett
                Cellular & Molecular Biology Letters
                BioMed Central (London )
                1425-8153
                1689-1392
                19 August 2022
                19 August 2022
                2022
                : 27
                : 70
                Affiliations
                GRID grid.24696.3f, ISNI 0000 0004 0369 153X, Beijing Key Laboratory of Basic Research With Traditional Chinese Medicine On Infectious Diseases, Beijing Institute of Chinese Medicine, Beijing Hospital of Traditional Chinese Medicine, , Capital Medical University, ; Beijing, 100010 China
                Author information
                http://orcid.org/0000-0003-1354-1343
                Article
                368
                10.1186/s11658-022-00368-y
                9392286
                35986232
                b4bc166e-d009-4649-8794-6f918235cb53
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 10 May 2022
                : 1 August 2022
                Funding
                Funded by: Beijing Construction Program for High-level Public Health of Technical Talents
                Award ID: 2022-3-009
                Award Recipient :
                Funded by: Beijing Natural Science Foundation
                Award ID: 7182071
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81503399
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2022

                mirna,bacterial pneumonia,host–pathogen,sensitivity,specificity,off-target effect

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