Gata3驱动miR-21-5p转录以减轻高氧诱导的肺损伤，独立于CpG岛甲基化。

IF 3.9 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Scientific Reports Pub Date : 2025-07-04 DOI:10.1038/s41598-025-09039-2

Yingcong Ren, Song Qin, Ping Yuan, Qianxia Huang, Ma Huang, Yuanzhi Shi, Miao Chen

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引用次数: 0

摘要

microRNA-21-5p （miR-21-5p）在高氧诱导的肺损伤（HALI）中起关键的抗凋亡作用，但其调控机制尚不清楚。本研究发现Gata3是一种新的上游转录因子，可增强miR-21-5p的表达。生物信息学分析和GEO转录组学数据显示Gata3和miR-21-5p水平呈正相关。值得注意的是，miR-21-5p启动子缺乏CpG岛，表明转录调控独立于甲基化。Gata3促进miR-21-5p转录，减少肺泡上皮细胞凋亡，缓解HALI。此外，在miR-21-5p敲除小鼠中，Gata3过表达未能减轻HALI，这突出了miR-21-5p在Gata3介导的肺保护中的关键作用。本研究揭示了miRNA调控的一种新的转录机制，为HALI的发病机制提供了有价值的见解。

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Gata3 drives miR-21-5p transcription to mitigate hyperoxia-induced lung injury, independent of CpG Island methylation.

microRNA-21-5p (miR-21-5p) plays a key anti-apoptotic role in hyperoxia-induced lung injury (HALI), but its regulatory mechanisms are not well understood. This study identified Gata3 as a novel upstream transcription factor that enhanced miR-21-5p expression. Bioinformatic analyses and GEO transcriptomic data revealed a positive correlation between Gata3 and miR-21-5p levels. Notably, the miR-21-5p promoter lacked a CpG island, indicating transcriptional regulation independent of methylation. Gata3 promoted miR-21-5p transcription, reduced apoptosis in alveolar epithelial cells and alleviating HALI. Furthermore, Gata3 overexpression failed to mitigate HALI in miR-21-5p knockout mice, highlighting the critical role of miR-21-5p in Gata3-mediated lung protection. This study uncovered a novel transcriptional mechanism for miRNA regulation, providing valuable insights into the pathogenesis of HALI.

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来源期刊

Scientific Reports Natural Science Disciplines-

CiteScore

7.50

自引率

4.30%

发文量

19567

审稿时长

3.9 months

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