{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T03:26:46Z","timestamp":1790306806777,"version":"4.1.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T00:00:00Z","timestamp":1695168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100004761","name":"Natural Science Foundation of Hainan Province of China","doi-asserted-by":"crossref","award":["821MS121"],"award-info":[{"award-number":["821MS121"]}],"id":[{"id":"10.13039\/501100004761","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Hainan Province Clinical Medical Center"},{"name":"Hainan General Hospital National Natural Science Foundation Cultivation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Uncontrolled proliferation of pulmonary artery smooth muscle cells (PASMCs) contributes to the pathogenesis of pulmonary arterial hypertension (PAH). In this work, we defined the precise part of circ_0068481 in PASMC proliferation and migration induced by hypoxia. We hypothesized that circ_0068481 enhanced hypoxia-induced PASMC proliferation, invasion, and migration through the microRNA (miR)-361-3p\/Kr\u00fcppel-like factor 5 (KLF5) pathway.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Human PASMCs (hPASMCs) were exposed to hypoxic (3% O2) conditions. Circ_0068481, miR-361-3p, and KLF5 levels were gauged by qRT-PCR and western blot. Cell viability, proliferation, invasion, and migration were detected by XTT, EdU incorporation, transwell, and wound-healing assays, respectively. Dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays were performed to confirm the direct relationship between miR-361-3p and circ_0068481 or KLF5.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Circ_0068481 expression was increased in the serum of PAH patients and hypoxia-induced hPASMCs. Downregulation of circ_0068481 attenuated hypoxia-induced promotion in hPASMC proliferation, invasion, and migration. Circ_0068481 directly targeted miR-361-3p, and miR-361-3p downregulation reversed the inhibitory effects of circ_0068481 silencing on hypoxia-induced hPASMC proliferation, invasion, and migration. KLF5 was a direct miR-361-3p target, and miR-361-3p upregulation mitigated hypoxia-induced hPASMC proliferation, invasion, and migration by inhibiting KLF5 expression. Moreover, circ_0068481-induced KLF5 expression by binding to miR-361-3p in hypoxic hPASMCs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Circ_0068481 knockdown ameliorated hypoxia-induced hPASMC proliferation, invasion, and migration at least in part through the miR-361-3p\/KLF5 axis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ajh\/hpad028","type":"journal-article","created":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T17:43:15Z","timestamp":1695404595000},"page":"33-45","source":"Crossref","is-referenced-by-count":4,"title":["Circ_0068481 Affects the Human Pulmonary Artery Smooth Muscle Cells\u2019 Progression by miR-361-3p\/KLF5 Axis"],"prefix":"10.1093","volume":"37","author":[{"given":"Hai-Rong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Cardiology, Hainan Affiliated Hospital of Hainan Medical University , Hainan General Hospital , Haikou , China"},{"name":"The Second School of Clinical Medicine, Southern Medical University , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guan-Liang","family":"Chen","sequence":"additional","affiliation":[{"name":"The Second School of Clinical Medicine, Southern Medical University , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Li","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hainan Affiliated Hospital of Hainan Medical University , Hainan General Hospital , Haikou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing-Jiu","family":"Cai","sequence":"additional","affiliation":[{"name":"The Second School of Clinical Medicine, Southern Medical University , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong-Li","family":"Xu","sequence":"additional","affiliation":[{"name":"The Second School of Clinical Medicine, Southern Medical University , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Dong","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory department, Hainan Affiliated Hospital of Hainan Medical University , Hainan General Hospital , Haikou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hainan Affiliated Hospital of Hainan Medical University , Hainan General Hospital , Haikou , China"},{"name":"Department of Pediatric Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,9,20]]},"reference":[{"key":"2023121606093991100_CIT0001","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s11886-019-1235-4","article-title":"Pulmonary arterial 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