{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T15:16:52Z","timestamp":1786375012901,"version":"build-2736575974"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T00:00:00Z","timestamp":1636329600000},"content-version":"vor","delay-in-days":311,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>. Circular RNA phosphorylase kinase regulatory subunit alpha 2 (circPHKA2; hsa_circ_0090002) has a significantly, specifically different expression in acute ischemic stroke (AIS) patients\u2019 blood. Here, we intended to investigate the role and mechanism of circPHKA2 in oxygen\u2010glucose deprivation\u2010 (OGD\u2010) induced stoke model in human brain microvascular endothelial cells (HBMEC). <jats:italic>Methods<\/jats:italic>. Expression of circPHKA2, microRNA\u2010 (miR\u2010) 574\u20105p, and superoxide dismutase\u20102 (SOD2) was detected by quantitative PCR and western blotting. Cell injury was measured by detecting cell proliferation (EdU assay and CCK\u20108 assay), migration (transwell assay), neovascularization (tube formation assay), apoptosis (flow cytometry and western blotting), endoplasmic reticulum stress (western blotting), and oxidative stress (assay kits). Direct intermolecular interaction was determined by bioinformatics algorithms, dual\u2010luciferase reporter assay, biotin\u2010labelled miRNA capture, and argonaute 2 RNA immunoprecipitation. <jats:italic>Results<\/jats:italic>. circPHKA2 was downregulated in AIS patients\u2019 blood in SOD2\u2010correlated manner. Reexpressing circPHKA2 rescued EdU incorporation, cell viability and migration, tube formation, B cell lymphoma\u20102 (Bcl\u20102) expression, and SOD activity of OGD\u2010induced HBMEC and alleviate apoptotic rate and levels of Bcl\u20102\u2010associated protein (Bax), glucose\u2010regulated protein 78\u2009kD (GRP78), C\/EBP\u2010homologous protein (CHOP), caspase\u201012, reactive oxygen species (ROS), and malondialdehyde (MDA). Additionally, blocking SOD2 partially attenuated these roles of circPHKA2 overexpression. Molecularly, circPHKA2 upregulated SOD2 expression via interacting with miR\u2010574\u20105p, and miR\u2010574\u20105p could target SOD2. Similarly, allied to neurovascular protection of circPHKA2 was the downregulation of miR\u2010574\u20105p. <jats:italic>Conclusion<\/jats:italic>. circPHKA2 could protect HBMEC against OGD\u2010induced cerebral stroke model via the miR\u2010574\u20105p\/SOD2 axis, suggesting circPHKA2 as a novel and promising candidate in ischemic brain injury.<\/jats:p>","DOI":"10.1155\/2021\/3823122","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:50:05Z","timestamp":1636419005000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Circular RNA circPHKA2 Relieves OGD\u2010Induced Human Brain Microvascular Endothelial Cell Injuries through Competitively Binding miR\u2010574\u20105p to Modulate 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