YY1-induced Long non-coding RNA HOXA11-AS activates oxidative stress and inflammation by epigenetic modification of Nrf2 pathway to promote keloid formation
Background Long non-coding RNAs (lncRNAs) are increasingly recognized in keloid pathogenesis. This study investigates the role and mechanisms of HOXA11-AS in keloid formation.Methods Expression levels of HOXA11-AS and related proteins were measured in keloid tissues and fibroblasts using qRT-PCR, We...
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Taylor & Francis Group
2025-12-01
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| Series: | Redox Report |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/13510002.2025.2539030 |
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| author | Jun Jin Kai Wang Chenxi Lu Chenghao Yao Feng Xie |
| author_facet | Jun Jin Kai Wang Chenxi Lu Chenghao Yao Feng Xie |
| author_sort | Jun Jin |
| collection | DOAJ |
| description | Background Long non-coding RNAs (lncRNAs) are increasingly recognized in keloid pathogenesis. This study investigates the role and mechanisms of HOXA11-AS in keloid formation.Methods Expression levels of HOXA11-AS and related proteins were measured in keloid tissues and fibroblasts using qRT-PCR, Western blot, and ELISA. Functional assays assessed cell proliferation, migration, fibrosis, and oxidative stress. RIP, ChIP, Co-IP, FISH, and luciferase assays were used to explore interactions among HOXA11-AS, YY1, Nrf2, EZH2, and DNMT1. An in vivo mouse xenograft model validated the findings.Results HOXA11-AS was upregulated in keloids. Silencing HOXA11-AS reduced fibroblast proliferation, migration, fibrosis, and oxidative stress. Its overexpression had the opposite effect, which was reversed by Nrf2 pathway inhibition. HOXA11-AS promoted the methylation of the Nrf2 promoter via DNMT1 recruitment, mediated by EZH2. YY1 enhanced HOXA11-AS transcription by binding to its promoter. The YY1/HOXA11-AS axis was confirmed in vivo.Conclusion YY1-induced HOXA11-AS drives keloid formation by promoting oxidative stress and inflammation through epigenetic suppression of Nrf2 signaling. |
| format | Article |
| id | doaj-art-a389ff2fc9504e198c0f8c0aa7955ef1 |
| institution | DOAJ |
| issn | 1351-0002 1743-2928 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Redox Report |
| spelling | doaj-art-a389ff2fc9504e198c0f8c0aa7955ef12025-08-20T03:05:42ZengTaylor & Francis GroupRedox Report1351-00021743-29282025-12-0130110.1080/13510002.2025.2539030YY1-induced Long non-coding RNA HOXA11-AS activates oxidative stress and inflammation by epigenetic modification of Nrf2 pathway to promote keloid formationJun Jin0Kai Wang1Chenxi Lu2Chenghao Yao3Feng Xie4Department of Plastic Surgery, Henan Provincial People’s Hospital (Zhengzhou University People’s Hospital), Zhengzhou, People’s Republic of ChinaDepartment of Plastic Surgery, Henan Provincial People’s Hospital (Zhengzhou University People’s Hospital), Zhengzhou, People’s Republic of ChinaDepartment of Plastic Surgery, Henan Provincial People’s Hospital (Zhengzhou University People’s Hospital), Zhengzhou, People’s Republic of ChinaDepartment of Plastic Surgery, Henan Provincial People’s Hospital (Zhengzhou University People’s Hospital), Zhengzhou, People’s Republic of ChinaDepartment of Plastic Surgery, Henan Provincial People’s Hospital (Zhengzhou University People’s Hospital), Zhengzhou, People’s Republic of ChinaBackground Long non-coding RNAs (lncRNAs) are increasingly recognized in keloid pathogenesis. This study investigates the role and mechanisms of HOXA11-AS in keloid formation.Methods Expression levels of HOXA11-AS and related proteins were measured in keloid tissues and fibroblasts using qRT-PCR, Western blot, and ELISA. Functional assays assessed cell proliferation, migration, fibrosis, and oxidative stress. RIP, ChIP, Co-IP, FISH, and luciferase assays were used to explore interactions among HOXA11-AS, YY1, Nrf2, EZH2, and DNMT1. An in vivo mouse xenograft model validated the findings.Results HOXA11-AS was upregulated in keloids. Silencing HOXA11-AS reduced fibroblast proliferation, migration, fibrosis, and oxidative stress. Its overexpression had the opposite effect, which was reversed by Nrf2 pathway inhibition. HOXA11-AS promoted the methylation of the Nrf2 promoter via DNMT1 recruitment, mediated by EZH2. YY1 enhanced HOXA11-AS transcription by binding to its promoter. The YY1/HOXA11-AS axis was confirmed in vivo.Conclusion YY1-induced HOXA11-AS drives keloid formation by promoting oxidative stress and inflammation through epigenetic suppression of Nrf2 signaling.https://www.tandfonline.com/doi/10.1080/13510002.2025.2539030KeloidHOXA11-ASYY1Nrf2oxidative stressinflammation |
| spellingShingle | Jun Jin Kai Wang Chenxi Lu Chenghao Yao Feng Xie YY1-induced Long non-coding RNA HOXA11-AS activates oxidative stress and inflammation by epigenetic modification of Nrf2 pathway to promote keloid formation Redox Report Keloid HOXA11-AS YY1 Nrf2 oxidative stress inflammation |
| title | YY1-induced Long non-coding RNA HOXA11-AS activates oxidative stress and inflammation by epigenetic modification of Nrf2 pathway to promote keloid formation |
| title_full | YY1-induced Long non-coding RNA HOXA11-AS activates oxidative stress and inflammation by epigenetic modification of Nrf2 pathway to promote keloid formation |
| title_fullStr | YY1-induced Long non-coding RNA HOXA11-AS activates oxidative stress and inflammation by epigenetic modification of Nrf2 pathway to promote keloid formation |
| title_full_unstemmed | YY1-induced Long non-coding RNA HOXA11-AS activates oxidative stress and inflammation by epigenetic modification of Nrf2 pathway to promote keloid formation |
| title_short | YY1-induced Long non-coding RNA HOXA11-AS activates oxidative stress and inflammation by epigenetic modification of Nrf2 pathway to promote keloid formation |
| title_sort | yy1 induced long non coding rna hoxa11 as activates oxidative stress and inflammation by epigenetic modification of nrf2 pathway to promote keloid formation |
| topic | Keloid HOXA11-AS YY1 Nrf2 oxidative stress inflammation |
| url | https://www.tandfonline.com/doi/10.1080/13510002.2025.2539030 |
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