FTO deficiency facilitates epithelia dysfunction in oral lichen planus
The fat mass and obesity-associated protein (FTO) is identified as regulating mammalian development and diseases by removing methyl groups from RNAs. However, the roles of FTO in the context of oral lichen planus (OLP) remain unknown. Here, we demonstrated that the protein levels of FTO in the kerat...
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| Language: | English |
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Elsevier
2025-03-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253125000174 |
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| author | Yufeng Fan Yukai Hao Yan Ding Xiangyu Wang Xuejun Ge |
| author_facet | Yufeng Fan Yukai Hao Yan Ding Xiangyu Wang Xuejun Ge |
| author_sort | Yufeng Fan |
| collection | DOAJ |
| description | The fat mass and obesity-associated protein (FTO) is identified as regulating mammalian development and diseases by removing methyl groups from RNAs. However, the roles of FTO in the context of oral lichen planus (OLP) remain unknown. Here, we demonstrated that the protein levels of FTO in the keratinocytes from OLP patients were down-regulated compared to those from healthy participants. At the molecular level, we explained that GSK-3β-induced phosphorylation promoted FTO protein degradation in diseased oral keratinocytes. Using a cell co-culture model, we further confirmed that FTO deficiency facilitated NF-κB activation and apoptosis in oral keratinocytes under inflammatory conditions. Vitamin D receptor (VDR), which plays a protective role in OLP, was mediated by FTO in an RNA N6-methyladenosine (m6A) methylation-dependent way. FTO overexpression failed to suppress NF-κB and caspase-3 activities upon VDR ablation in oral keratinocytes, suggesting that FTO insufficiency damages oral epithelial by targeting VDR. Collectively, these data reveal that FTO deficiency facilitates epithelial dysfunction in OLP by decreasing VDR expression. |
| format | Article |
| id | doaj-art-98c884c0efff40b6af3954c17f81d230 |
| institution | Kabale University |
| issn | 2162-2531 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj-art-98c884c0efff40b6af3954c17f81d2302025-02-07T04:47:26ZengElsevierMolecular Therapy: Nucleic Acids2162-25312025-03-01361102463FTO deficiency facilitates epithelia dysfunction in oral lichen planusYufeng Fan0Yukai Hao1Yan Ding2Xiangyu Wang3Xuejun Ge4Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China; Department of Endodontics, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, ChinaShanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China; Department of Endodontics, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, ChinaDepartment of Dermatology, Hainan Provincial Hospital of Skin Disease, Haikou, Hainan, China; Department of Dermatology, Skin Disease Hospital of Hainan Medical University, Haikou, Hainan, ChinaShanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, ChinaShanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China; Department of Endodontics, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China; Corresponding author: Xuejun Ge, Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, NO. 63 Xinjian South Road, Taiyuan, Shanxi 030001, China.The fat mass and obesity-associated protein (FTO) is identified as regulating mammalian development and diseases by removing methyl groups from RNAs. However, the roles of FTO in the context of oral lichen planus (OLP) remain unknown. Here, we demonstrated that the protein levels of FTO in the keratinocytes from OLP patients were down-regulated compared to those from healthy participants. At the molecular level, we explained that GSK-3β-induced phosphorylation promoted FTO protein degradation in diseased oral keratinocytes. Using a cell co-culture model, we further confirmed that FTO deficiency facilitated NF-κB activation and apoptosis in oral keratinocytes under inflammatory conditions. Vitamin D receptor (VDR), which plays a protective role in OLP, was mediated by FTO in an RNA N6-methyladenosine (m6A) methylation-dependent way. FTO overexpression failed to suppress NF-κB and caspase-3 activities upon VDR ablation in oral keratinocytes, suggesting that FTO insufficiency damages oral epithelial by targeting VDR. Collectively, these data reveal that FTO deficiency facilitates epithelial dysfunction in OLP by decreasing VDR expression.http://www.sciencedirect.com/science/article/pii/S2162253125000174MT: RNA and epigenetic editing Special Issuefat mass and obesity-associated proteinoral lichen planusvitamin D receptorRNA m6A modificationoral epithelial dysfunction |
| spellingShingle | Yufeng Fan Yukai Hao Yan Ding Xiangyu Wang Xuejun Ge FTO deficiency facilitates epithelia dysfunction in oral lichen planus Molecular Therapy: Nucleic Acids MT: RNA and epigenetic editing Special Issue fat mass and obesity-associated protein oral lichen planus vitamin D receptor RNA m6A modification oral epithelial dysfunction |
| title | FTO deficiency facilitates epithelia dysfunction in oral lichen planus |
| title_full | FTO deficiency facilitates epithelia dysfunction in oral lichen planus |
| title_fullStr | FTO deficiency facilitates epithelia dysfunction in oral lichen planus |
| title_full_unstemmed | FTO deficiency facilitates epithelia dysfunction in oral lichen planus |
| title_short | FTO deficiency facilitates epithelia dysfunction in oral lichen planus |
| title_sort | fto deficiency facilitates epithelia dysfunction in oral lichen planus |
| topic | MT: RNA and epigenetic editing Special Issue fat mass and obesity-associated protein oral lichen planus vitamin D receptor RNA m6A modification oral epithelial dysfunction |
| url | http://www.sciencedirect.com/science/article/pii/S2162253125000174 |
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