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      MicroRNA-5195-3p alleviates high glucose‑induced injury in human ARPE-19 cells by targeting GMFB

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      PLoS ONE
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          Abstract

          Hyperglycemia is generally considered to be an important cause of diabetic retinopathy (DR). The aim of the present study was to investigate the role of miR-5195-3p in high glucose (HG)-induced human retinal pigment epithelial ARPE-19 cell injury. Here, we first found that the expression level of miR-5195-3p was significantly downregulated in HG-stimulated ARPE-19 cells using reverse transcription quantitative PCR. Overexpression of miR-5195-3p attenuated the impaired cell viability, increased apoptosis and pro-inflammatory cytokines secretion in ARPE-19 cells under HG condition using CCK-8 assay, flow cytometry and ELISA assay, respectively. Luciferase reporter assay showed that miR-5195-3p could specifically bind to the 3’UTR of glia maturation factor-β (GMFB). GMFB overexpression reversed, while knockdown enhanced the protective effects of miR-5195-3p overexpression against HG-induced ARPE-19 cell injury. In summary, miR-5195-3p targeting GMFB might be a potential therapeutic target for DR.

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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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            Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?

            MicroRNAs constitute a large family of small, approximately 21-nucleotide-long, non-coding RNAs that have emerged as key post-transcriptional regulators of gene expression in metazoans and plants. In mammals, microRNAs are predicted to control the activity of approximately 30% of all protein-coding genes, and have been shown to participate in the regulation of almost every cellular process investigated so far. By base pairing to mRNAs, microRNAs mediate translational repression or mRNA degradation. This Review summarizes the current understanding of the mechanistic aspects of microRNA-induced repression of translation and discusses some of the controversies regarding different modes of microRNA function.
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              Mammalian microRNAs predominantly act to decrease target mRNA levels

              Summary MicroRNAs (miRNAs) are endogenous ∼22-nucleotide RNAs that play important gene-regulatory roles by pairing to the mRNAs of protein-coding genes to direct their repression. Repression of these regulatory targets leads to decreased translational efficiency and/or decreased mRNA levels, but the relative contributions of these two outcomes have been largely unknown, particularly for endogenous targets expressed at low-to-moderate levels. Here, we use ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on mRNA levels. For both ectopic and endogenous miRNA regulatory interactions, lowered mRNA levels account for most (≥84%) of the decreased protein production. These results show that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Supervision
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: MethodologyRole: Project administration
                Role: InvestigationRole: SoftwareRole: Writing – original draft
                Role: SoftwareRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                18 November 2021
                2021
                : 16
                : 11
                : e0260071
                Affiliations
                [001] Eye Hospital, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
                University of Florida, UNITED STATES
                Author notes

                Competing Interests: The authors declare that they have no competing interests.

                Author information
                https://orcid.org/0000-0002-3362-8270
                Article
                PONE-D-21-06097
                10.1371/journal.pone.0260071
                8601420
                34793551
                b1bc9c8f-4fdf-4b12-bc23-2636864995e0
                © 2021 Liu et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 23 February 2021
                : 2 November 2021
                Page count
                Figures: 5, Tables: 0, Pages: 11
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Biology and Life Sciences
                Cell Biology
                Cell Processes
                Cell Death
                Apoptosis
                Biology and Life Sciences
                Molecular Biology
                Molecular Biology Techniques
                Transfection
                Research and Analysis Methods
                Molecular Biology Techniques
                Transfection
                Biology and Life Sciences
                Molecular Biology
                Molecular Biology Techniques
                Molecular Biology Assays and Analysis Techniques
                Gene Expression and Vector Techniques
                Hyperexpression Techniques
                Research and Analysis Methods
                Molecular Biology Techniques
                Molecular Biology Assays and Analysis Techniques
                Gene Expression and Vector Techniques
                Hyperexpression Techniques
                Physical Sciences
                Chemistry
                Chemical Compounds
                Organic Compounds
                Carbohydrates
                Monosaccharides
                Glucose
                Physical Sciences
                Chemistry
                Organic Chemistry
                Organic Compounds
                Carbohydrates
                Monosaccharides
                Glucose
                Research and Analysis Methods
                Bioassays and Physiological Analysis
                Cell Analysis
                Cell Viability Testing
                Biology and Life Sciences
                Immunology
                Immune Response
                Inflammation
                Medicine and Health Sciences
                Immunology
                Immune Response
                Inflammation
                Medicine and Health Sciences
                Clinical Medicine
                Signs and Symptoms
                Inflammation
                Medicine and Health Sciences
                Medical Conditions
                Metabolic Disorders
                Hyperglycemia
                Biology and life sciences
                Biochemistry
                Nucleic acids
                RNA
                Non-coding RNA
                Natural antisense transcripts
                MicroRNAs
                Biology and life sciences
                Genetics
                Gene expression
                Gene regulation
                MicroRNAs
                Custom metadata
                All relevant data are included in the manuscript.

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