Gata3 drives miR-21-5p transcription to mitigate hyperoxia-induced lung injury, independent of CpG Island methylation
Abstract 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...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-09039-2 |
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| Summary: | Abstract 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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| ISSN: | 2045-2322 |