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      MicroRNAs play an essential role in autophagy regulation in various disease phenotypes

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          Abstract

          Autophagy is a highly conserved catabolic process and fundamental biological process in eukaryotic cells. It recycles intracellular components to provide nutrients during starvation and maintains quality control of organelles and proteins. In addition, autophagy is a well‐organized homeostatic cellular process that is responsible for the removal of damaged organelles and intracellular pathogens. Moreover, it also modulates the innate and adaptive immune systems. Micro ribonucleic acids (microRNAs) are a mature class of post‐transcriptional modulators that are widely expressed in tissues and organs. And, it can suppress gene expression by targeting messenger RNAs for translational repression or, at a lesser extent, degradation. Research indicates that microRNAs regulate autophagy through different pathways, playing an essential role in the treatment of various diseases. It is an important regulator of fundamental cellular processes such as proliferation, autophagy, and cell apoptosis. In this review article, we first review the current knowledge of autophagy and the function of microRNAs. Then, we summarize the mechanism of autophagy and the signaling pathways related to autophagy by citing at least the main proteins involved in the different phases of the process. Second, we introduce other members of RNA and report some examples in various pathologies. Finally, we review the current literature regarding microRNA‐based therapies for cancer, atherosclerosis, cardiac disease, tuberculosis, and viral diseases. MicroRNAs can cause autophagy upregulation or downregulation by targeting genes or affecting autophagy‐related signaling pathways. Therefore, the microRNAs have a huge potential in autophagy regulation, and it is the function as diagnostic and prognostic markers.

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          Most cited references109

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          LC3 conjugation system in mammalian autophagy

          Autophagy is the bulk degradation of proteins and organelles, a process essential for cellular maintenance, cell viability, differentiation and development in mammals. Autophagy has significant associations with neurodegenerative diseases, cardiomyopathies, cancer, programmed cell death, and bacterial and viral infections. During autophagy, a cup-shaped structure, the preautophagosome, engulfs cytosolic components, including organelles, and closes, forming an autophagosome, which subsequently fuses with a lysosome, leading to the proteolytic degradation of internal components of the autophagosome by lysosomal lytic enzymes. During the formation of mammalian autophagosomes, two ubiquitylation-like modifications are required, Atg12-conjugation and LC3-modification. LC3 is an autophagosomal ortholog of yeast Atg8. A lipidated form of LC3, LC3-II, has been shown to be an autophagosomal marker in mammals, and has been used to study autophagy in neurodegenerative and neuromuscular diseases, tumorigenesis, and bacterial and viral infections. The other Atg8 homologues, GABARAP and GATE-16, are also modified by the same mechanism. In non-starved rats, the tissue distribution of LC3-II differs from those of the lipidated forms of GABARAP and GATE-16, GABARAP-II and GATE-16-II, suggesting that there is a functional divergence among these three modified proteins. Delipidation of LC3-II and GABARAP-II is mediated by hAtg4B. We review the molecular mechanism of LC3-modification, the crosstalk between LC3-modification and mammalian Atg12-conjugation, and the cycle of LC3-lipidation and delipidation mediated by hAtg4B, as well as recent findings concerning the other two Atg8 homologues, GABARAP and GATE-16. We also highlight recent findings regarding the pathobiology of LC3-modification, including its role in microbial infection, cancer and neuromuscular diseases.
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            A Brief Review on the Mechanisms of miRNA Regulation

            MicroRNAs (miRNAs) are a class of short, endogenously-initiated non-coding RNAs that post-transcriptionally control gene expression via either translational repression or mRNA degradation. It is becoming evident that miRNAs are playing significant roles in regulatory mechanisms operating in various organisms, including developmental timing and host-pathogen interactions as well as cell differentiation, proliferation, apoptosis and tumorigenesis. Likewise, as a regulatory element, miRNA itself is coordinatively modulated by multifarious effectors when carrying out basic functions, such as SNP, miRNA editing, methylation and circadian clock. This mini-review summarized the current understanding of interactions between miRNAs and their targets, including recent advancements in deciphering the regulatory mechanisms that control the biogenesis and functionality of miRNAs in various cellular processes.
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              Autophagy during viral infection — a double-edged sword

              Autophagy is a powerful tool that host cells use to defend against viral infection. Double-membrane vesicles, termed autophagosomes, deliver trapped viral cargo to the lysosome for degradation. Specifically, autophagy initiates an innate immune response by cooperating with pattern recognition receptor signalling to induce interferon production. It also selectively degrades immune components associated with viral particles. Following degradation, autophagy coordinates adaptive immunity by delivering virus-derived antigens for presentation to T lymphocytes. However, in an ongoing evolutionary arms race, viruses have acquired the potent ability to hijack and subvert autophagy for their benefit. In this Review, we focus on the key regulatory steps during viral infection in which autophagy is involved and discuss the specific molecular mechanisms that diverse viruses use to repurpose autophagy for their life cycle and pathogenesis.
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                Author and article information

                Contributors
                wenhui.changchun@163.com
                Journal
                Biofactors
                Biofactors
                10.1002/(ISSN)1872-8081
                BIOF
                Biofactors (Oxford, England)
                John Wiley & Sons, Inc. (Hoboken, USA )
                0951-6433
                1872-8081
                16 August 2019
                Nov-Dec 2019
                : 45
                : 6 ( doiID: 10.1002/biof.v45.6 )
                : 844-856
                Affiliations
                [ 1 ] Laboratory of Pathogenic Microbiology and Immunology College of Life Science, Jilin Agricultural University Changchun China
                [ 2 ] Ministry of Education, Engineering Research Center for Bioreactor and Pharmaceutical Development Jilin Agricultural University Changchun China
                Author notes
                [*] [* ] Correspondence

                Wenhui Zhang, Laboratory of Pathogenic Microbiology and Immunology, College of Life Science, Jilin Agricultural University, No. 2888 Xincheng Street, Jingyue Development Zone, Changchun City, Jilin Province, 130118, China.

                Email: wenhui.changchun@ 123456163.com

                Author information
                https://orcid.org/0000-0002-8961-373X
                Article
                BIOF1555
                10.1002/biof.1555
                6916288
                31418958
                adeb6a06-bcf7-4e33-ac94-04ea1c8a0a5a
                © 2019 The Authors. BioFactors published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 June 2019
                : 31 July 2019
                Page count
                Figures: 0, Tables: 5, Pages: 13, Words: 10813
                Funding
                Funded by: Jilin Province Science and Technology Development Plan Project
                Award ID: 20180101256JC
                Award ID: 20180101264JC
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                November/December 2019
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.3 mode:remove_FC converted:17.12.2019

                Molecular biology
                autophagy,disease,micrornas,regulation
                Molecular biology
                autophagy, disease, micrornas, regulation

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