{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:10:54Z","timestamp":1790691054682,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T00:00:00Z","timestamp":1614038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology in Taiwan","award":["MOST 106-2314-B-040 -001 -MY3"],"award-info":[{"award-number":["MOST 106-2314-B-040 -001 -MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Oral submucous fibrosis (OSF) is known as a potentially malignant disorder, which may result from chemical irritation due to areca nuts (such as arecoline). Emerging evidence suggests that fibrogenesis and carcinogenesis are regulated by the interaction of long noncoding RNAs (lncRNAs) and microRNAs. Among these regulators, profibrotic lncRNA H19 has been found to be overexpressed in several fibrosis diseases. Here, we examined the expression of H19 in OSF specimens and its functional role in fibrotic buccal mucosal fibroblasts (fBMFs). Our results indicate that the aberrantly overexpressed H19 contributed to higher myofibroblast activities, such as collagen gel contractility and migration ability. We also demonstrated that H19 interacted with miR-29b, which suppressed the direct binding of miR-29b to the 3\u2032-untranslated region of type I collagen (COL1A1). We showed that ectopic expression of miR-29b ameliorated various myofibroblast phenotypes and the expression of \u03b1-smooth muscle actin (\u03b1-SMA), COL1A1, and fibronectin (FN1) in fBMFs. In OSF tissues, we found that the expression of miR-29b was downregulated and there was a negative correlation between miR-29b and these fibrosis markers. Lastly, we demonstrate that arecoline stimulated the upregulation of H19 through the transforming growth factor (TGF)-\u03b2 pathway. Altogether, this study suggests that increased TGF-\u03b2 secretion following areca nut chewing may induce the upregulation of H19, which serves as a natural sponge for miR-29b and impedes its antifibrotic effects.<\/jats:p>","DOI":"10.3390\/ijms22042216","type":"journal-article","created":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T12:40:16Z","timestamp":1614084016000},"page":"2216","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Targeting lncRNA H19\/miR-29b\/COL1A1 Axis Impedes Myofibroblast Activities of Precancerous Oral Submucous Fibrosis"],"prefix":"10.3390","volume":"22","author":[{"given":"Cheng-Chia","family":"Yu","sequence":"first","affiliation":[{"name":"Institute of Oral Sciences, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Dentistry, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"},{"name":"School of Dentistry, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Wen","family":"Liao","sequence":"additional","affiliation":[{"name":"Institute of Oral Sciences, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"School of Dentistry, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Ling","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, China Medical University, Taichung 404333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9731-2577","authenticated-orcid":false,"given":"Yu-Chao","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"},{"name":"School of Dentistry, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1111\/j.1600-0714.2007.00582.x","article-title":"Nomenclature and classification of potentially malignant disorders of the oral mucosa","volume":"36","author":"Warnakulasuriya","year":"2007","journal-title":"J. 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