{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T04:50:45Z","timestamp":1776401445592,"version":"3.51.2"},"reference-count":85,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T00:00:00Z","timestamp":1656979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology","award":["MOST110-2314-B-038-045-MY2"],"award-info":[{"award-number":["MOST110-2314-B-038-045-MY2"]}]},{"name":"Ministry of Science and Technology","award":["111-wf-eva-06"],"award-info":[{"award-number":["111-wf-eva-06"]}]},{"name":"Wan Fang Hospital","award":["MOST110-2314-B-038-045-MY2"],"award-info":[{"award-number":["MOST110-2314-B-038-045-MY2"]}]},{"name":"Wan Fang Hospital","award":["111-wf-eva-06"],"award-info":[{"award-number":["111-wf-eva-06"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Oral submucous fibrosis (OSF) is a chronic fibrotic remodeling disease that can progress to oral cancer. However, efficient clinical diagnosis and treatment methods for OSF are still lacking. This study investigated the anti-fibrotic effect of fucoidan on oral fibrosis. To evaluate the fibrotic ability (myofibroblast activities), we performed wound-healing, Transwell migration, and collagen contraction assays by using patient-derived normal and fibrotic buccal submucous fibroblasts (BMFs and fBMFs, respectively). RNA-sequencing and dual-luciferase reporter and RNA immunoprecipitation chip assays were performed to identify the clinical significance and molecular mechanism of non-coding RNAs. Fucoidan suppressed the myofibroblast activities and inhibited the MEG3 in fBMFs. MEG3 was overexpressed in the OSF tissue and was positively associated with myofibroblast markers. Knockdown of MEG3 markedly inhibited myofibroblast activities, which were restored by inhibiting miR-181a and overexpressing Egr1. The results from luciferase reporter and RIP assays confirmed that MEG3 functioned as a competing endogenous RNA (ceRNA) and could directly target miR-181a, thereby preventing the miR-181a-mediated translational repression of Egr1. This study demonstrated that MEG3 exerts a profibrotic effect on OSF by targeting miR-181a\/Egr1. Therefore, the administration of fucoidan may serve as a potential therapeutic strategy for OSF by targeting the overexpression of MEG3.<\/jats:p>","DOI":"10.3390\/ph15070833","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T05:41:06Z","timestamp":1657086066000},"page":"833","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Fucoidan-Mediated Inhibition of Fibrotic Properties in Oral Submucous Fibrosis via the MEG3\/miR-181a\/Egr1 Axis"],"prefix":"10.3390","volume":"15","author":[{"given":"Chih-Yuan","family":"Fang","sequence":"first","affiliation":[{"name":"School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Division of Oral and Maxillofacial Surgery, Department of Dentistry, Wan Fang Hospital, Taipei 116, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Szu-Han","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Dentistry, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3285-0523","authenticated-orcid":false,"given":"Chun-Chung","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Oral Sciences, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Wen","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0920-9340","authenticated-orcid":false,"given":"Shih-Chi","family":"Chao","sequence":"additional","affiliation":[{"name":"Institute of Oral Sciences, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Medical Research and Education, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan 265501, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng-Chia","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Dentistry, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Institute of Oral Sciences, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Dentistry, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.oraloncology.2008.05.016","article-title":"Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classification and present concepts of management","volume":"45","year":"2009","journal-title":"Oral Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10006-010-0219-8","article-title":"Areca nut in pathogenesis of oral submucous fibrosis: Revisited","volume":"15","author":"Angadi","year":"2011","journal-title":"Oral Maxillofac. 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