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      MicroRNA-21-5p Reduces Hypoxia/Reoxygenation-Induced Neuronal Cell Damage through Negative Regulation of CPEB3

      research-article
      1 , 1 , 2 , , 3
      Analytical Cellular Pathology (Amsterdam)
      Hindawi

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          Abstract

          Objectives

          To explore the role of microRNA-21-5p (miR-21-5p) in hypoxia/reoxygenation- (H/R-) induced HT22 cell damage.

          Methods

          The hypoxia/reoxygenation (H/R) model was established in mouse neuronal cells HT22. Cell Counting Kit-8 (CCK-8) and qRT-PCR were used to determine the effects of H/R treatment on cell viability and miR-21-5p expression. HT22 cells were transfected with miR-21-5p mimic or negative control (NC) followed by the induction of H/R; cell viability, apoptosis, and SOD, MDA, and LDH activities were detected. Besides, the apoptosis-related proteins including BAX, BCL2, cleaved caspase-3, and caspase-3 as well as proteins of EGFR/PI3K/AKT signaling pathways were measured by Western blot. To verify the target relation between cytoplasmic polyadenylation element binding protein 3 (CPEB3) and miR-21-5p, luciferase reporter gene experiment was performed. After cotransfection with miR-21-5p mimic and CPEB3 plasmids, the reversal effects of CPEB3 on miR-21-5p in H/R damage were studied.

          Results

          H/R treatment could significantly reduce the cell viability ( P < 0.05) and miR-21-5p levels ( P < 0.05) in HT22 cells. After overexpressing miR-21-5p, cell viability was increased ( P < 0.05) under H/R treatment, and the apoptosis rate and the levels of apoptosis-related proteins were suppressed (all P < 0.05). Furthermore, SOD activity was increased ( P < 0.05), while MDA and LDH activity was decreased (both P < 0.05). Besides, miR-21-5p could restore the activation of the EGFR/PI3K/AKT signaling pathway inhibited by H/R treatment (all P < 0.05). The luciferase reporter gene experiment verified that CPEB3 is the target of miR-21-5p ( P < 0.05). When coexpressing miR-21-5p mimic and CPEB3 in the cells, the protective effects of miR-21-5p under H/R were reversed (all P < 0.05), and the activation of the EGFR/PI3K/AKT pathway was also inhibited (all P < 0.05).

          Conclusion

          This study showed that miR-21-5p may regulate the EGFR/PI3K/AKT signaling pathway by targeting CPEB3 to reduce H/R-induced cell damage and apoptosis.

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          Most cited references26

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          An overview of microRNAs: Biology, functions, therapeutics, and analysis methods

          MicroRNAs (miRNAs) are a class of small noncoding RNAs, which function in posttranscriptional regulation of gene expression. They are powerful regulators of various cellular activities including cell growth, differentiation, development, and apoptosis. They have been linked to many diseases, and currently miRNA-mediated clinical trial has shown promising results for treatment of cancer and viral infection. This review provides an overview and update on miRNAs biogenesis, regulation of miRNAs expression, their biological functions, and role of miRNAs in epigenetics and cell-cell communication. In addition, alteration of miRNAs following exercise, their association with diseases, and therapeutic potential will be explained. Finally, miRNA bioinformatics tools and conventional methods for miRNA detection and quantification will be discussed.
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            Effects of trichothecene mycotoxins on eukaryotic cells: a review.

            The major products of the trichothecene mycotoxin biosynthetic pathway produced in a species- and sometimes isolate-specific manner by cereal-pathogenic Fusarium fungi include T-2 toxin, diacetoxyscirpenol, deoxynivalenol and nivalenol. This paper briefly reviews the major effects of such trichothecenes on the gross morphology, cytology and molecular signalling within eukaryotic cells. The gross toxic effects of select trichothecenes on animals include growth retardation, reduced ovarian function and reproductive disorders, immuno-compromization, feed refusal and vomiting. The phytotoxic effects of deoxynivalenol on plants can be summarized as growth retardation, inhibition of seedling and green plant regeneration. Trichothecenes are now recognized as having multiple inhibitory effects on eukaryote cells, including inhibition of protein, DNA and RNA synthesis, inhibition of mitochondrial function, effects on cell division and membrane effects. In animal cells, they induce apoptosis, a programmed cell death response. Current knowledge about the eukaryotic signal transduction cascades and downstream gene products activated by trichothecenes is limited, especially in plants. In mammalian cells, certain trichothecenes trigger a ribotoxic stress response and activate mitogen-activated protein kinases. DON mediates the inflammatory response by modulating the binding activities of specific transcription factors and subsequently inducing cytokine gene expression. Several genes are up-regulated in wheat in response to trichothecene mycotoxins; the significance, if any, of these genes in the host response to trichothecenes has yet to be elucidated.
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              MicroRNAs: history, biogenesis, and their evolving role in animal development and disease.

              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.
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                Author and article information

                Contributors
                Journal
                Anal Cell Pathol (Amst)
                Anal Cell Pathol (Amst)
                acp
                Analytical Cellular Pathology (Amsterdam)
                Hindawi
                2210-7177
                2210-7185
                2021
                2 December 2021
                : 2021
                : 5543212
                Affiliations
                1Department of Neurology, Affiliated Hospital of Weifang Medical College, Weifang, Shandong 261031, China
                2Pain Department, Weifang People's Hospital, Weifang, Shandong 261041, China
                3Department of Plastic Surgery, Plastic Surgery Hospital of Weifang Medical University, Weifang, Shandong 261042, China
                Author notes

                Academic Editor: Dorota L. Stankowska

                Author information
                https://orcid.org/0000-0003-1891-0689
                https://orcid.org/0000-0002-0146-8057
                Article
                10.1155/2021/5543212
                8660214
                34900520
                07f789ec-842d-436e-ab81-bc0d491b80e2
                Copyright © 2021 Bin Wang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 January 2021
                : 4 September 2021
                : 7 November 2021
                Funding
                Funded by: Shandong Province Medicine and Health Technology Development Plan
                Award ID: 2018WS062
                Categories
                Research Article

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