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      Roles of Calcium Regulating MicroRNAs in Cardiac Ischemia-Reperfusion Injury

      review-article
      Author(s): 1 , 2 , 1 , 2 , 1 , 2 , *
      Publication date (Electronic):
      Journal: Cells
      Publisher: MDPI
      Keywords: microRNA, calcium, Ca2+, myocardial ischemia-reperfusion injury, heart

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          Abstract

          Cardiac Ca 2+ cycling and signaling are closely associated with cardiac function. Changes in cellular Ca 2+ homeostasis may lead to aberrant cardiac rhythm and may play a critical role in the pathogenesis of cardiac diseases, due to their exacerbation of heart failure. MicroRNAs (miRNAs) play a key role in the regulation of gene expression at the post-transcriptional level and participate in regulating diverse biological processes. The emerging evidence indicates that the expression profiles of miRNAs vary among human diseases, including cardiovascular diseases. Cardiac Ca 2+-handling and signaling proteins are also regulated by miRNAs. Given the relationship between cardiac Ca 2+ homeostasis and signaling and miRNA, Ca 2+-related miRNAs may serve as therapeutic targets during the treatment of heart failure. In this review, we summarize the knowledge currently available regarding the role of Ca 2+ in cardiac function, as well as changes in Ca 2+ cycling and homeostasis and the handling of these processes by miRNAs during cardiac ischemia-reperfusion injury.

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          Circulating microRNAs: Association with disease and potential use as biomarkers.

          Glen Reid, Michaela Kirschner, Nico van Zandwijk (2011)
          The control of gene expression by microRNAs influences many cellular processes and has been implicated in the control of many (patho)physiological states. Recently, microRNAs have been detected in serum and plasma, and circulating microRNA profiles have now been associated with a range of different tumour types, diseases such as stroke and heart disease, as well as altered physiological states such as pregnancy. Here we review the disease-specific profiles of circulating microRNAs, and the methodologies used for their detection and quantification. We also discuss possible functions of circulating microRNAs and their potential as non-invasive biomarkers. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
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            Inhibition of miR-15 protects against cardiac ischemic injury.

            Nedra L. Montgomery, Eric Olson, Eva Van den Bussche … (2012)
            Myocardial infarction (MI) is a leading cause of death worldwide. Because endogenous cardiac repair mechanisms are not sufficient for meaningful tissue regeneration, MI results in loss of cardiac tissue and detrimental remodeling events. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression in a sequence dependent manner. Our previous data indicate that miRNAs are dysregulated in response to ischemic injury of the heart and actively contribute to cardiac remodeling after MI. This study was designed to determine whether miRNAs are dysregulated on ischemic damage in porcine cardiac tissues and whether locked nucleic acid (LNA)-modified anti-miR chemistries can target cardiac expressed miRNAs to therapeutically inhibit miR-15 on ischemic injury. Our data indicate that the miR-15 family, which includes 6 closely related miRNAs, is regulated in the infarcted region of the heart in response to ischemia-reperfusion injury in mice and pigs. LNA-modified chemistries can effectively silence miR-15 family members in vitro and render cardiomyocytes resistant to hypoxia-induced cardiomyocyte cell death. Correspondingly, systemic delivery of miR-15 anti-miRs dose-dependently represses miR-15 in cardiac tissue of both mice and pigs, whereas therapeutic targeting of miR-15 in mice reduces infarct size and cardiac remodeling and enhances cardiac function in response to MI. Oligonucleotide-based therapies using LNA-modified chemistries for modulating cardiac miRNAs in the setting of heart disease are efficacious and validate miR-15 as a potential therapeutic target for the manipulation of cardiac remodeling and function in the setting of ischemic injury.
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              Common features of microRNA target prediction tools

              Sarah M. Peterson, Jeffrey Thompson, Melanie Ufkin … (2014)
              The human genome encodes for over 1800 microRNAs (miRNAs), which are short non-coding RNA molecules that function to regulate gene expression post-transcriptionally. Due to the potential for one miRNA to target multiple gene transcripts, miRNAs are recognized as a major mechanism to regulate gene expression and mRNA translation. Computational prediction of miRNA targets is a critical initial step in identifying miRNA:mRNA target interactions for experimental validation. The available tools for miRNA target prediction encompass a range of different computational approaches, from the modeling of physical interactions to the incorporation of machine learning. This review provides an overview of the major computational approaches to miRNA target prediction. Our discussion highlights three tools for their ease of use, reliance on relatively updated versions of miRBase, and range of capabilities, and these are DIANA-microT-CDS, miRanda-mirSVR, and TargetScan. In comparison across all miRNA target prediction tools, four main aspects of the miRNA:mRNA target interaction emerge as common features on which most target prediction is based: seed match, conservation, free energy, and site accessibility. This review explains these features and identifies how they are incorporated into currently available target prediction tools. MiRNA target prediction is a dynamic field with increasing attention on development of new analysis tools. This review attempts to provide a comprehensive assessment of these tools in a manner that is accessible across disciplines. Understanding the basis of these prediction methodologies will aid in user selection of the appropriate tools and interpretation of the tool output.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cells
                Journal ID (iso-abbrev): Cells
                Journal ID (publisher-id): cells
                Title: Cells
                Publisher: MDPI
                ISSN (Electronic): 2073-4409
                Publication date (Electronic): 11 September 2014
                Publication date Collection: September 2014
                Volume: 3
                Issue: 3
                Pages: 899-913
                Affiliations
                [1 ]Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do 210-701, Korea; E-Mails: ehchoi@ 123456ish.or.kr (E.C.); mjcha@ 123456yuhs.ac (M.-J.C.)
                [2 ]Catholic Kwandong University International St. Mary’s Hospital, Incheon Metropolitan City 404-834, Korea
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: kchwang@ 123456cku.ac.kr or kchwang@ 123456ish.or.kr ; Tel.: +82-32-290-3883.
                Article
                Publisher ID: cells-03-00899
                DOI: 10.3390/cells3030899
                PMC ID: 4197635
                PubMed ID: 25216032
                SO-VID: 3ee43376-cf97-418f-adfa-297e401f04d7
                Copyright © © 2014 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 26 May 2014
                Date revision received : 02 September 2014
                Date accepted : 03 September 2014
                Categories
                Subject: Review

                Keywords: microrna,calcium,ca2+,myocardial ischemia-reperfusion injury,heart
                Data availability:
                Keywords: microrna, calcium, ca2+, myocardial ischemia-reperfusion injury, heart

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