METTL14 modulates the progression and ferroptosis of colitis by regulating the stability of m6A-modified GPX4
Abstract Ulcerative colitis (UC) is non-specific inflammatory bowel disease. UC development and progression were closely associated with epigenetic modifications. Nevertheless, the specific relationship between N6-methyladenosine (m6A) modification at RNA transcription levels and UC pathogenesis rem...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-02-01
|
| Series: | European Journal of Medical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40001-025-02334-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1825197364579663872 |
|---|---|
| author | Yuhua Chen Weicong Fan Ying Lyu Jingsheng Liao Ying Zhou |
| author_facet | Yuhua Chen Weicong Fan Ying Lyu Jingsheng Liao Ying Zhou |
| author_sort | Yuhua Chen |
| collection | DOAJ |
| description | Abstract Ulcerative colitis (UC) is non-specific inflammatory bowel disease. UC development and progression were closely associated with epigenetic modifications. Nevertheless, the specific relationship between N6-methyladenosine (m6A) modification at RNA transcription levels and UC pathogenesis remains unclear. We established UC cell models and mouse models through dextran sulfate sodium (DSS) induction. The expression levels of METTL14 were analyzed via qRT-PCR and western blot. In vitro functional experiments evaluated the effects of METTL14 overexpression on the viability of DSS-induced NCM460 cells and ferroptosis markers. Use of the m6A methylation detection kit, MeRIP-qPCR, and RNA stability experiments confirmed the molecular mechanism controlled by METTL14. In vivo experiments with inflammatory mice models elucidated the interaction between METTL14 and GPX4. Findings from this study indicated a notable reduction in m6A methyltransferase METTL14 expression in DSS-induced NCM460 cells and DSS-induced mice models. METTL14 overexpression effectively suppressed ferroptosis in DSS-induced NCM460 cells. In addition, METTL14 enhanced GPX4 mRNA stability through mediating m6A modification, and the interplay between METTL14 and GPX4 through m6A modification introduced innovative therapeutic approaches for UC management. |
| format | Article |
| id | doaj-art-8df37c2dc32f498d8c8f46032bae88c0 |
| institution | Kabale University |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-8df37c2dc32f498d8c8f46032bae88c02025-02-09T12:26:35ZengBMCEuropean Journal of Medical Research2047-783X2025-02-0130111210.1186/s40001-025-02334-8METTL14 modulates the progression and ferroptosis of colitis by regulating the stability of m6A-modified GPX4Yuhua Chen0Weicong Fan1Ying Lyu2Jingsheng Liao3Ying Zhou4Anorectal Department, Dongguan Hospital of Traditional Chinese MedicineAnorectal Department, Dongguan Hospital of Traditional Chinese MedicineAnorectal Department, Dongguan Hospital of Traditional Chinese MedicineMedical Oncology, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital)Anorectal Department, Dongguan Hospital of Traditional Chinese MedicineAbstract Ulcerative colitis (UC) is non-specific inflammatory bowel disease. UC development and progression were closely associated with epigenetic modifications. Nevertheless, the specific relationship between N6-methyladenosine (m6A) modification at RNA transcription levels and UC pathogenesis remains unclear. We established UC cell models and mouse models through dextran sulfate sodium (DSS) induction. The expression levels of METTL14 were analyzed via qRT-PCR and western blot. In vitro functional experiments evaluated the effects of METTL14 overexpression on the viability of DSS-induced NCM460 cells and ferroptosis markers. Use of the m6A methylation detection kit, MeRIP-qPCR, and RNA stability experiments confirmed the molecular mechanism controlled by METTL14. In vivo experiments with inflammatory mice models elucidated the interaction between METTL14 and GPX4. Findings from this study indicated a notable reduction in m6A methyltransferase METTL14 expression in DSS-induced NCM460 cells and DSS-induced mice models. METTL14 overexpression effectively suppressed ferroptosis in DSS-induced NCM460 cells. In addition, METTL14 enhanced GPX4 mRNA stability through mediating m6A modification, and the interplay between METTL14 and GPX4 through m6A modification introduced innovative therapeutic approaches for UC management.https://doi.org/10.1186/s40001-025-02334-8ColitisMETTL14m6AGPX4Ferroptosis |
| spellingShingle | Yuhua Chen Weicong Fan Ying Lyu Jingsheng Liao Ying Zhou METTL14 modulates the progression and ferroptosis of colitis by regulating the stability of m6A-modified GPX4 European Journal of Medical Research Colitis METTL14 m6A GPX4 Ferroptosis |
| title | METTL14 modulates the progression and ferroptosis of colitis by regulating the stability of m6A-modified GPX4 |
| title_full | METTL14 modulates the progression and ferroptosis of colitis by regulating the stability of m6A-modified GPX4 |
| title_fullStr | METTL14 modulates the progression and ferroptosis of colitis by regulating the stability of m6A-modified GPX4 |
| title_full_unstemmed | METTL14 modulates the progression and ferroptosis of colitis by regulating the stability of m6A-modified GPX4 |
| title_short | METTL14 modulates the progression and ferroptosis of colitis by regulating the stability of m6A-modified GPX4 |
| title_sort | mettl14 modulates the progression and ferroptosis of colitis by regulating the stability of m6a modified gpx4 |
| topic | Colitis METTL14 m6A GPX4 Ferroptosis |
| url | https://doi.org/10.1186/s40001-025-02334-8 |
| work_keys_str_mv | AT yuhuachen mettl14modulatestheprogressionandferroptosisofcolitisbyregulatingthestabilityofm6amodifiedgpx4 AT weicongfan mettl14modulatestheprogressionandferroptosisofcolitisbyregulatingthestabilityofm6amodifiedgpx4 AT yinglyu mettl14modulatestheprogressionandferroptosisofcolitisbyregulatingthestabilityofm6amodifiedgpx4 AT jingshengliao mettl14modulatestheprogressionandferroptosisofcolitisbyregulatingthestabilityofm6amodifiedgpx4 AT yingzhou mettl14modulatestheprogressionandferroptosisofcolitisbyregulatingthestabilityofm6amodifiedgpx4 |