Mechanism of LncRNA CBR3-AS1 in regulating pyroptosis of intestinal epithelial cells in ulcerative colitis.

IF 2.9 4区生物学 Q2 BIOPHYSICS

Journal of Bioenergetics and Biomembranes Pub Date : 2025-04-21 DOI:10.1007/s10863-025-10060-3

Xi Li, Caiwen Yan, Suxia Li, Lujun Shen, Lijuan Huo

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引用次数: 0

Abstract

Ulcerative colitis (UC) is a common chronic relapsing inflammatory disease that threatens human life. This study aims to explore the mechanism of LncRNA CBR3-AS1 in pyroptosis of intestinal epithelial cells in UC. The levels of CBR3-AS1, KLF2, and SUGT1 in UC cells were detected. After downregulating CBR3-AS1 expression, cell viability and pyroptosis were measured, followed by the detection of SOD and MDA levels. The binding of CBR3-AS1 to EZH2, enrichment of EZH2 and H3K27me3 on the KLF2 promoter, and binding of KLF2 to the SUGT1 promoter were assayed. The role of CBR3-AS1 in pyroptosis was validated in animal models. We found that CBR3-AS1 and SUGT1 were increased in UC cells, and KLF2 was decreased. After downregulation of CBR3-AS1, cell viability was increased and pyroptosis was alleviated. CBR3-AS1 recruited EZH2 to occupy the KLF2 promoter, leading to increased H3K27me3 levels and suppressed KLF2 expression, reducing the enrichment of KLF2 on the SUGT1 promoter, finally promoting SUGT1 expression. SUGT1 overexpression or KLF2 downregulation alleviated the protective effect of silencing CBR3-AS1 on pyroptosis in UC cells. CBR3-AS1 downregulation alleviates cell pyroptosis in colonic tissues. In conclusion, CBR3-AS1 exacerbated pyroptosis of intestinal epithelial cells in UC via the KLF2/SUGT1 pathway.

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LncRNA CBR3-AS1调控溃疡性结肠炎肠上皮细胞焦亡的机制

溃疡性结肠炎（UC）是一种常见的慢性复发性炎症性疾病，威胁着人类的生命安全。本研究旨在探讨LncRNA CBR3-AS1在UC肠上皮细胞焦亡中的作用机制。检测UC细胞中CBR3-AS1、KLF2、SUGT1水平。下调CBR3-AS1表达后，测定细胞活力和焦亡率，检测SOD和MDA水平。研究了CBR3-AS1与EZH2的结合、EZH2和H3K27me3在KLF2启动子上的富集以及KLF2与SUGT1启动子的结合。在动物模型中验证了CBR3-AS1在焦亡中的作用。我们发现CBR3-AS1和SUGT1在UC细胞中升高，KLF2降低。下调CBR3-AS1后，细胞活力增加，焦亡减轻。CBR3-AS1招募EZH2占据KLF2启动子，导致H3K27me3水平升高，抑制KLF2表达，减少了KLF2在SUGT1启动子上的富集，最终促进了SUGT1的表达。SUGT1过表达或KLF2下调可减轻沉默CBR3-AS1对UC细胞焦亡的保护作用。下调CBR3-AS1可减轻结肠组织细胞焦亡。综上所述，CBR3-AS1通过KLF2/SUGT1通路加重UC中肠上皮细胞的焦亡。

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来源期刊

Journal of Bioenergetics and Biomembranes 生物-生物物理

CiteScore

6.00

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The Journal of Bioenergetics and Biomembranes is an international journal devoted to the publication of original research that contributes to fundamental knowledge in the areas of bioenergetics, biomembranes, and transport, including oxidative phosphorylation, photosynthesis, muscle contraction, as well as cellular and systemic metabolism. The timely research in this international journal benefits biophysicists, membrane biologists, cell biologists, biochemists, molecular biologists, physiologists, endocrinologists, and bio-organic chemists.