{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:47:09Z","timestamp":1787014029859,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:00:00Z","timestamp":1658966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771155"],"award-info":[{"award-number":["81771155"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91849130"],"award-info":[{"award-number":["91849130"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2021QH016"],"award-info":[{"award-number":["ZR2021QH016"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To explore the expression changes and roles of the RNA\u2010binding protein RCAN1.1 in acute ischemic stroke (AIS), and to preliminarily confirm the medicinal value of the RNA aptamer R1SR13 in AIS by targeting RCAN1.1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two mouse AIS models of middle cerebral artery occlusion (MCAO) and right common carotid artery ligation (R\u2010CCAL) and oxygen glucose deprivation (OGD) model of AIS in primary neurons and SH\u2010SY5Y were performed. The expression pattern of RCAN1.1 was assessed using real\u2010time quantitative PCR (RT\u2010qPCR) and western blotting (WB) in vivo and in vitro. The underlying mechanism for the elevation of RCAN1.1 in the upstream was investigated. Lentiviruses were administrated and the effect of RCAN1.1 in AIS was assessed by ATP level, caspase 3\/7 assay, TUNEL and WB. The protective function of R1SR13 in AIS was evaluated both in vivo and in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In two mouse models of AIS,\n                      <jats:italic>RCAN1.1<\/jats:italic>\n                      mRNA and RCAN1.1\u00a0L protein were significantly upregulated in the ischemic brain tissue. The same results were detected in the OGD model of primary neurons and SH\u2010SY5Y. The mechanistic analysis proved that hypoxia\u2010inducible factor\u20101\u03b1 (HIF1\u03b1) could specifically activate the\n                      <jats:italic>RCAN1.1<\/jats:italic>\n                      gene promoter through combining with the functional hypoxia\u2010responsive element (HRE) site (\u2212325\u2009to\u2009\u2212322\u2009bp). The increased expression of RCAN1.1\u00a0L markedly depleted ATP production and aggravated neuronal apoptosis under OGD condition. R1SR13, an antagonizing RNA aptamer of RCAN1.1, was demonstrated to reduce neuronal apoptosis caused by the elevated RCAN1.1\u00a0L in the cellular and animal models of AIS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>RCAN1.1<\/jats:italic>\n                      is a novel target gene of HIF1\u03b1 and the functional HRE in the RCAN1.1 promoter region is \u2212325\u2009to\u2009\u2212322\u2009bp. The marked upregulation of RCAN1.1 in AIS promoted neuronal apoptosis, an effect that could be reversed by its RNA aptamer R1SR13 in vivo and in vitro. Thus, R1SR13 represents a promising strategy for neuroprotection in AIS and our study lays a theoretical foundation for it to become a clinically targeted drug.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.13921","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T15:45:49Z","timestamp":1659023149000},"page":"1814-1828","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Targeting upregulated RNA binding protein RCAN1.1: a promising strategy for neuroprotection in acute ischemic stroke"],"prefix":"10.1111","volume":"28","author":[{"given":"Yan","family":"Yun","sequence":"first","affiliation":[{"name":"Department of Radiology Qilu Hospital of Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaxin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology Qilu Hospital of Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shichuan","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Neurology Qilu Hospital of Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin","family":"Wang","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Otorhinolaryngology Qilu Hospital of Shandong University  Jinan China"},{"name":"Department of Otorhinolaryngology Qilu Hospital of Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbin","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Neurology Qilu Hospital of Shandong University  Jinan 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