{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:00:51Z","timestamp":1792706451905,"version":"4.5.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Micro\n              <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n              (miRNA) is a type of noncoding\n              <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n              that can repress the expression of target genes through posttranscriptional regulation. In addition to numerous physiologic roles for mi\n              <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n              s, they play an important role in pathophysiologic processes affecting cardiovascular health. Previously, we reported that nuclear encoded microRNA (miR\u2010181c) is present in heart mitochondria, and importantly, its overexpression affects mitochondrial function by regulating mitochondrial gene expression.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              To investigate further how the miR\u2010181 family affects the heart, we suppressed miR\u2010181 using a miR\u2010181\u2010sponge containing 10 repeated complementary miR\u2010181 \u201cseed\u201d sequences and generated a set of H9c2 cells, a cell line derived from rat myoblast, by stably expressing either a scrambled or miR\u2010181\u2010sponge sequence. Sponge\u2010H9c2 cells showed a decrease in reactive oxygen species production and reduced basal mitochondrial respiration and protection against doxorubicin\u2010induced oxidative stress. We also found that miR\u2010181a\/b targets phosphatase and tensin homolog (\n              <jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content>\n              ), and the sponge\u2010expressing stable cells had increased\n              <jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content>\n              activity and decreased\n              <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>\n              3K signaling. In addition, we have used miR\u2010181a\/b\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              and miR\u2010181c\/d\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              knockout mice and subjected them to ischemia\u2010reperfusion injury. Our results suggest divergent effects of different miR\u2010181 family members: miR\u2010181a\/b targets\n              <jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content>\n              in the cytosol, resulting in an increase in infarct size in miR\u2010181a\/b\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice due to increased\n              <jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content>\n              signaling, whereas miR\u2010181c targets mt\u2010\n              <jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\n              1 in the mitochondria, resulting in decreased infarct size in miR\u2010181c\/d\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              The miR\u2010181 family alters the myocardial response to oxidative stress, notably with detrimental effects by targeting mt\u2010\n              <jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\n              1 (miR\u2010181c) or with protection by targeting\n              <jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content>\n              (miR\u2010181a\/b).\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.116.004694","type":"journal-article","created":{"date-parts":[[2017,2,28]],"date-time":"2017-02-28T01:30:32Z","timestamp":1488245432000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":92,"title":["Divergent Effects of miR\u2010181 Family Members on Myocardial Function Through Protective Cytosolic and Detrimental Mitochondrial microRNA Targets"],"prefix":"10.1161","volume":"6","author":[{"given":"Samarjit","family":"Das","sequence":"first","affiliation":[{"name":"Department of Pathology Johns Hopkins School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Kohr","sequence":"additional","affiliation":[{"name":"Department of Environmental Health and Engineering Bloomberg School of Public Health Johns Hopkins University Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany","family":"Dunkerly\u2010Eyring","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong I.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Cardiology Johns Hopkins School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djahida","family":"Bedja","sequence":"additional","affiliation":[{"name":"Department of Cardiology Johns Hopkins School of Medicine Baltimore MD"},{"name":"Faculty of Medicine and Health Sciences Macquarie University Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver A.","family":"Kent","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre University of Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony K. L.","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Bloomberg School of Public Health Johns Hopkins University Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Henao\u2010Mejia","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Perelman School of Medicine University of Pennsylvania Philadelphia PA"},{"name":"Division of Transplant Immunology Department of Pathology and Laboratory Medicine Children's Hospital of Philadelphia University of Pennsylvania Philadelphia PA"},{"name":"Institute for Immunology Perelman School of Medicine Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Flavell","sequence":"additional","affiliation":[{"name":"Department of Immunobiology Yale University School of Medicine New Haven 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