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

IF 7.4 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Report Pub Date : 2025-12-01 Epub Date: 2025-08-12 DOI:10.1080/13510002.2025.2539030

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

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引用次数: 0

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.

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yy1诱导的长链非编码RNA HOXA11-AS通过表观遗传修饰Nrf2通路激活氧化应激和炎症，促进瘢痕疙瘩形成。

背景：长链非编码rna （lncRNAs）在瘢痕疙瘩发病机制中得到越来越多的认识。本研究探讨了HOXA11-AS在瘢痕疙瘩形成中的作用和机制。方法：采用qRT-PCR、Western blot和ELISA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。功能分析评估细胞增殖、迁移、纤维化和氧化应激。采用RIP、ChIP、Co-IP、FISH和荧光素酶检测HOXA11-AS、YY1、Nrf2、EZH2和DNMT1之间的相互作用。体内小鼠异种移植模型证实了这一发现。结果：HOXA11-AS在瘢痕疙瘩中表达上调。沉默HOXA11-AS可减少成纤维细胞增殖、迁移、纤维化和氧化应激。其过表达具有相反的作用，通过Nrf2通路抑制可以逆转。HOXA11-AS通过EZH2介导的DNMT1募集促进Nrf2启动子的甲基化。YY1通过结合其启动子增强HOXA11-AS的转录。YY1/HOXA11-AS轴在体内得到证实。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，从而驱动瘢痕疙瘩的形成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Redox Report 生物-生化与分子生物学

CiteScore

6.10

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Redox Report is a multidisciplinary peer-reviewed open access journal focusing on the role of free radicals, oxidative stress, activated oxygen, perioxidative and redox processes, primarily in the human environment and human pathology. Relevant papers on the animal and plant environment, biology and pathology will also be included. While emphasis is placed upon methodological and intellectual advances underpinned by new data, the journal offers scope for review, hypotheses, critiques and other forms of discussion.