{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T04:34:26Z","timestamp":1785645266055,"version":"3.56.0"},"reference-count":27,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,10,7]],"date-time":"2020-10-07T00:00:00Z","timestamp":1602028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81741096"],"award-info":[{"award-number":["81741096"]}],"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":["81701501"],"award-info":[{"award-number":["81701501"]}],"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":["81770513"],"award-info":[{"award-number":["81770513"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>Long non\u2010coding RNAs (lncRNAs) are widely involved in the progression of Hirschsprung's disease (HSCR), but the role of actin filament associated protein\u00a01 antisense RNA1 (<jats:italic>AFAP1\u2010AS1<\/jats:italic>), an lncRNA, in HSCR has not been explored before.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>Downregulation of <jats:italic>AFAP1\u2010AS1<\/jats:italic> blocks enteric neural crest stem cell proliferation, differentiation, migration and invasion and promotes the occurrence of HSCR via the <jats:italic>miR\u2010195\/E2F3<\/jats:italic> axis, indicating that<jats:italic>AFAP1\u2010AS<\/jats:italic> might be a potential biomarker for HSCR patients.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Long non\u2010coding RNAs (lncRNAs) are involved in several human disorders. Nevertheless, it remains unclear whether they are implicated in the phenotypes of enteric neural crest stem cells (ENCSCs) in Hirschsprung's disease (HSCR). Therefore, we designed this study to explore the pathogenicity of <jats:italic>AFAP1\u2010AS1<\/jats:italic> for HSCR. Microarray analysis and bioinformatic tools were used to screen out the differentially lncRNAs and microRNAs (miRNAs) in patients with HSCR. Small interference RNA transfection was applied to carry out functional experiments in ENCSCs. Cellular activities were detected by cell counting kit\u20108, 5\u2010ethynyl\u20102\u2032\u2010deoxyuridine, Transwell assays and flow cytometry. Finally, rescue experiments were performed to examine the cofunction of <jats:italic>AFAP1\u2010AS1<\/jats:italic> and <jats:italic>miR\u2010195<\/jats:italic> and of <jats:italic>miR\u2010195<\/jats:italic> and E2F transcription factor 3 (<jats:italic>E2F3<\/jats:italic>). <jats:italic>AFAP1\u2010AS1<\/jats:italic> was reduced in HSCR patients. Meanwhile, knockdown of <jats:italic>AFAP1\u2010AS1<\/jats:italic> reduced the cell migratory and proliferative capacities and facilitated cell apoptosis along with G0\/G1 phase arrest. <jats:italic>E2F3<\/jats:italic> was diminished when <jats:italic>miR\u2010195<\/jats:italic> was upregulated, and <jats:italic>AFAP1\u2010AS1<\/jats:italic> inhibition reduced its ability to bind to <jats:italic>miR\u2010195<\/jats:italic>. Altogether, <jats:italic>AFAP1\u2010AS1<\/jats:italic> silencing acts as an endogenous RNA by interacting with <jats:italic>miR\u2010195<\/jats:italic> to alter <jats:italic>E2F3<\/jats:italic> expression, thus conferring repressive effects on ENCSC activity and promoting HSCR progression.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep088780","type":"journal-article","created":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T11:55:12Z","timestamp":1600775712000},"page":"1939-1949","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Involvement of the lncRNA AFAP1\u2010AS1\/microRNA\u2010195\/E2F3 axis in proliferation and migration of enteric neural crest stem cells of Hirschsprung's disease"],"prefix":"10.1113","volume":"105","author":[{"given":"Weikang","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery the Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi PR 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