Fucoidan-Mediated Inhibition of Fibrotic Properties in Oral Submucous Fibrosis via the MEG3/miR-181a/Egr1 Axis
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 abil...
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| Format: | Article |
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MDPI AG
2022-07-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/7/833 |
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| author | Chih-Yuan Fang Szu-Han Chen Chun-Chung Huang Yi-Wen Liao Shih-Chi Chao Cheng-Chia Yu |
| author_facet | Chih-Yuan Fang Szu-Han Chen Chun-Chung Huang Yi-Wen Liao Shih-Chi Chao Cheng-Chia Yu |
| author_sort | Chih-Yuan Fang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T10:13:47Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T10:13:47Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-bf55b6753a1541bcbc4b43b60d5043772023-12-01T22:33:25ZengMDPI AGPharmaceuticals1424-82472022-07-0115783310.3390/ph15070833Fucoidan-Mediated Inhibition of Fibrotic Properties in Oral Submucous Fibrosis via the MEG3/miR-181a/Egr1 AxisChih-Yuan Fang0Szu-Han Chen1Chun-Chung Huang2Yi-Wen Liao3Shih-Chi Chao4Cheng-Chia Yu5School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110, TaiwanSchool of Dentistry, Chung Shan Medical University, Taichung 40201, TaiwanInstitute of Oral Sciences, Chung Shan Medical University, Taichung 40201, TaiwanDepartment of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, TaiwanInstitute of Oral Sciences, Chung Shan Medical University, Taichung 40201, TaiwanSchool of Dentistry, Chung Shan Medical University, Taichung 40201, TaiwanOral 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.https://www.mdpi.com/1424-8247/15/7/833oral submucous fibrosisMEG3miR-181aEgr1myofibroblastscompeting endogenous RNA |
| spellingShingle | Chih-Yuan Fang Szu-Han Chen Chun-Chung Huang Yi-Wen Liao Shih-Chi Chao Cheng-Chia Yu Fucoidan-Mediated Inhibition of Fibrotic Properties in Oral Submucous Fibrosis via the MEG3/miR-181a/Egr1 Axis Pharmaceuticals oral submucous fibrosis MEG3 miR-181a Egr1 myofibroblasts competing endogenous RNA |
| title | Fucoidan-Mediated Inhibition of Fibrotic Properties in Oral Submucous Fibrosis via the MEG3/miR-181a/Egr1 Axis |
| title_full | Fucoidan-Mediated Inhibition of Fibrotic Properties in Oral Submucous Fibrosis via the MEG3/miR-181a/Egr1 Axis |
| title_fullStr | Fucoidan-Mediated Inhibition of Fibrotic Properties in Oral Submucous Fibrosis via the MEG3/miR-181a/Egr1 Axis |
| title_full_unstemmed | Fucoidan-Mediated Inhibition of Fibrotic Properties in Oral Submucous Fibrosis via the MEG3/miR-181a/Egr1 Axis |
| title_short | Fucoidan-Mediated Inhibition of Fibrotic Properties in Oral Submucous Fibrosis via the MEG3/miR-181a/Egr1 Axis |
| title_sort | fucoidan mediated inhibition of fibrotic properties in oral submucous fibrosis via the meg3 mir 181a egr1 axis |
| topic | oral submucous fibrosis MEG3 miR-181a Egr1 myofibroblasts competing endogenous RNA |
| url | https://www.mdpi.com/1424-8247/15/7/833 |
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