CircPCNX1-mediated Regulation of Pulmonary Artery Smooth Muscle Cell Proliferation and Migration in Rat Model of High Pulmonary Blood Flow-induced Pulmonary Arterial Hypertension

CircPCNX1-mediated Regulation of Pulmonary Artery Smooth Muscle Cell Proliferation and Migration in Rat Model of High Pulmonary Blood Flow-induced Pulmonary Arterial Hypertension | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article CircPCNX1-mediated Regulation of Pulmonary Artery Smooth Muscle Cell Proliferation and Migration in Rat Model of High Pulmonary Blood Flow-induced Pulmonary Arterial Hypertension Yuqin Huang, Danyan Su, Bingbing Ye, Yanyun Huang, Dongli Liu, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8563718/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract In this study, we investigate the regulatory role of the circular RNA circPCNX1 in modulating the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) under high pulmonary blood flow-induced pulmonary arterial hypertension (PAH). A rat model of PAH was established via abdominal aorta-inferior vena cava shunting. The circular structure and subcellular localization of circPCNX1 were confirmed through Sanger sequencing, RNase R digestion assays, and fluorescence in situ hybridization. The expression level of circPCNX1 in PASMCs was verified by qRT-PCR. The effects of circPCNX1 on the proliferation and migration of PASMCs were explored through lentivirus transfection, cell-proliferation assays, and cell-scratch assays. The potential regulatory mechanism of circPCNX1 in the proliferation and migration of PASMCs was explored through online database prediction of combined microRNA (miRNA), RNA antisense purification, luciferase reporter assay, lentivirus transfection and gene-function enrichment test. We confirmed the circular structure of circPCNX1 and its cytoplasmic localization. circPCNX1 expression was downregulated in PASMCs of rats in high pulmonary blood flow-induced PAH. Functional experiments confirmed that overexpressed circPCNX1 inhibited PASMC proliferation and migration. RNA antisense purification and luciferase reporter assays demonstrated that circPCNX1 directly binds to miR-22-5p. Gene-function enrichment analysis revealed that the downstream target genes of miR-22-5p are predominantly enriched in the cGMP-PKG signaling pathway. Therefore, circPCNX1 regulates the proliferation and migration of PASMCs through direct interaction with miR-22-5p, and thereby modulates the cGMP-PKG signaling pathway. circPCNX1 migration proliferation pulmonary arterial hypertension Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8563718","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":578747548,"identity":"d9b515d6-9fef-4175-9266-b1383b6cdeb2","order_by":0,"name":"Yuqin Huang","email":"","orcid":"","institution":"Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yuqin","middleName":"","lastName":"Huang","suffix":""},{"id":578747550,"identity":"5522e340-6739-47b4-bd90-e6e6379e4964","order_by":1,"name":"Danyan Su","email":"","orcid":"","institution":"Department of 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Hypertension","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"circPCNX1, migration, proliferation, pulmonary arterial hypertension","lastPublishedDoi":"10.21203/rs.3.rs-8563718/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8563718/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIn this study, we investigate the regulatory role of the circular RNA \u003cem\u003ecircPCNX1\u003c/em\u003ein modulating the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) under high pulmonary blood flow-induced pulmonary arterial hypertension (PAH). A rat model of PAH was established via abdominal aorta-inferior vena cava shunting. The circular structure and subcellular localization of \u003cem\u003ecircPCNX1\u003c/em\u003e were confirmed through Sanger sequencing, RNase R digestion assays, and fluorescence in situ hybridization. The expression level of \u003cem\u003ecircPCNX1\u003c/em\u003e in PASMCs was verified by qRT-PCR. The effects of \u003cem\u003ecircPCNX1\u003c/em\u003e on the proliferation and migration of PASMCs were explored through lentivirus transfection, cell-proliferation assays, and cell-scratch assays. The potential regulatory mechanism of \u003cem\u003ecircPCNX1\u003c/em\u003e in the proliferation and migration of PASMCs was explored through online database prediction of combined microRNA (miRNA), RNA antisense purification, luciferase reporter assay, lentivirus transfection and gene-function enrichment test. We confirmed the circular structure of \u003cem\u003ecircPCNX1\u003c/em\u003eand its cytoplasmic localization. \u003cem\u003ecircPCNX1\u003c/em\u003e expression was downregulated in PASMCs of rats in high pulmonary blood flow-induced PAH. Functional experiments confirmed that overexpressed \u003cem\u003ecircPCNX1\u003c/em\u003e inhibited PASMC proliferation and migration. RNA antisense purification and luciferase reporter assays demonstrated that \u003cem\u003ecircPCNX1\u003c/em\u003e directly binds to miR-22-5p. Gene-function enrichment analysis revealed that the downstream target genes of miR-22-5p are predominantly enriched in the cGMP-PKG signaling pathway. Therefore, \u003cem\u003ecircPCNX1\u003c/em\u003e regulates the proliferation and migration of PASMCs through direct interaction with miR-22-5p, and thereby modulates the cGMP-PKG signaling pathway.\u003c/p\u003e","manuscriptTitle":"CircPCNX1-mediated Regulation of Pulmonary Artery Smooth Muscle Cell Proliferation and Migration in Rat Model of High Pulmonary Blood Flow-induced Pulmonary Arterial Hypertension","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-24 02:22:56","doi":"10.21203/rs.3.rs-8563718/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e93efd24-9d27-42d5-b6d5-5f87d783a069","owner":[],"postedDate":"January 24th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-08T18:09:40+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-24 02:22:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8563718","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8563718","identity":"rs-8563718","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}