The RNA m6A modification might participate in microglial activation during hypoxic-ischemic brain damage in neonatal mice

RNA m6A 修饰可能参与新生小鼠缺氧缺血性脑损伤期间小胶质细胞的活化

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作者:Xiaojuan Su, Lingyi Huang, Shiping Li, Junjie Ying, Fengyan Zhao, Shaopu Wang, Qian Liu, Yi Qu, Dezhi Mu

Background

The RNA m6A modification has been implicated in multiple neurological diseases as well as macrophage activation. However, whether it regulates microglial activation during hypoxic-ischemic brain damage (HIBD) in neonates remains unknown. Here, we

Conclusions

Our findings demonstrate that m6A modification of mRNA plays a crucial role in the regulation of microglial activation in HIBD, with m6A-associated regulators acting as key modulators of microglial activation.

Results

RNA-seq analysis revealed that, among 141 m6A regulators, 31 exhibited significant differential expression (FC (abs) ≥ 2) in HIBD mice. We then subjected the major m6A regulators Mettl3, Mettl14, Fto, Alkbh5, Ythdf1, and Ythdf2 to further validation, and the results showed that all were significantly downregulated in vitro and in vivo. GO analysis reveals that regulators are mainly involved in the regulation of cellular and metabolic processes. The KEGG results indicate the involvement of the signal transduction pathway. Conclusions: Our findings demonstrate that m6A modification of mRNA plays a crucial role in the regulation of microglial activation in HIBD, with m6A-associated regulators acting as key modulators of microglial activation.

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