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YY1诱导的长链非编码RNA HOXA11-AS通过对Nrf2通路进行表观遗传修饰激活氧化应激和炎症反应，从而促进瘢痕疙瘩形成。

YY1-induced Long non-coding RNA HOXA11-AS activates oxidative stress and inflammation by epigenetic modification of Nrf2 pathway to promote keloid formation.

作者信息

Jin Jun, Wang Kai, Lu Chenxi, Yao Chenghao, Xie Feng

机构信息

Department of Plastic Surgery, Henan Provincial People's Hospital (Zhengzhou University People's Hospital), Zhengzhou, People's Republic of China.

出版信息

Redox Rep. 2025 Dec;30(1):2539030. doi: 10.1080/13510002.2025.2539030. Epub 2025 Aug 12.

DOI:10.1080/13510002.2025.2539030
PMID:40799018
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12351724/
Abstract

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.

摘要

背景

长链非编码RNA（lncRNAs）在瘢痕疙瘩发病机制中的作用日益受到认可。本研究探讨HOXA11-AS在瘢痕疙瘩形成中的作用及机制。

方法

采用qRT-PCR、蛋白质免疫印迹法和酶联免疫吸附测定法检测瘢痕疙瘩组织和成纤维细胞中HOXA11-AS及相关蛋白的表达水平。功能试验评估细胞增殖、迁移、纤维化和氧化应激。采用RNA免疫沉淀、染色质免疫沉淀、免疫共沉淀、荧光原位杂交和荧光素酶测定法探讨HOXA11-AS、YY1、Nrf2、EZH2和DNMT1之间的相互作用。体内小鼠异种移植模型验证了研究结果。

结果

HOXA11-AS在瘢痕疙瘩中上调。沉默HOXA11-AS可降低成纤维细胞的增殖、迁移、纤维化和氧化应激。其过表达则产生相反的效果，而Nrf2通路抑制可逆转这种效果。HOXA11-AS通过EZH2介导招募DNMT1促进Nrf2启动子的甲基化。YY1通过结合其启动子增强HOXA11-AS转录。体内实验证实了YY1/HOXA11-AS轴。

结论

YY1诱导的HOXA11-AS通过表观遗传抑制Nrf2信号通路促进氧化应激和炎症反应，从而驱动瘢痕疙瘩形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/177f24dfdbc7/YRER_A_2539030_F0008_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/42a3ac478552/YRER_A_2539030_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/6b8fd2ec924b/YRER_A_2539030_F0002a_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/9b52276a279f/YRER_A_2539030_F0002b_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/bcbd2f2e5a01/YRER_A_2539030_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/66c57d3f99ad/YRER_A_2539030_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/a28a490f7ccb/YRER_A_2539030_F0005a_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/3b47201d3c66/YRER_A_2539030_F0005b_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/b290eadcb2cb/YRER_A_2539030_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/86cbf658e757/YRER_A_2539030_F0007a_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/26de5b3f0532/YRER_A_2539030_F0007b_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/177f24dfdbc7/YRER_A_2539030_F0008_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/42a3ac478552/YRER_A_2539030_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/6b8fd2ec924b/YRER_A_2539030_F0002a_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/9b52276a279f/YRER_A_2539030_F0002b_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/bcbd2f2e5a01/YRER_A_2539030_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/66c57d3f99ad/YRER_A_2539030_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/a28a490f7ccb/YRER_A_2539030_F0005a_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/3b47201d3c66/YRER_A_2539030_F0005b_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/b290eadcb2cb/YRER_A_2539030_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/86cbf658e757/YRER_A_2539030_F0007a_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/26de5b3f0532/YRER_A_2539030_F0007b_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d7/12351724/177f24dfdbc7/YRER_A_2539030_F0008_OC.jpg

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