METTL3/miR‐192‐5p/SCD1 Axis Regulates Lipid Metabolism to Affect T Cell Differentiation in Asthma

作者：Zhengrong Chen, Dongmei Yan, Suyu Guo, Yiyi Song, Xinxing Zhang, Wenjing Gu, Heting Dong, Li Huang · 发表于：Mediators of Inflammation · 年份：2025 · DOI：10.1155/mi/4955849 · 被引用次数：7 · 研究领域：RNA modifications and cancer、Cancer-related molecular mechanisms research、Cancer-related gene regulation

Background: This study aimed to explore the mechanisms underlying T‐cell differentiation in asthma. Methods and Results: Flow cytometry was performed to detect Th cells. LC‐MS/MS was performed to assess lipid metabolism. HE staining was performed to assess the pathological changes of the lung tissues. ELISA was performed to detect cytokine levels. The results of quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot showed that miR‐192‐5p expression was decreased, while SCD1 expression was increased in CD4 + T cells isolated from the peripheral blood of children with asthma. The dual luciferase reporter assay determined the direct interaction between miR‐192‐5p and SCD1. MiR‐192‐5p inhibitor reduced ASCL3 and PPARα, increased FASN and SREBP1c mRNA expression and protein levels in mouse spleen CD4 + T cells, and elevated Th2 and Th17 cells, but these effects were reversed by the SCD1 inhibitor. Oleic acid (OA) reduced Th1 cells and increased Th2 and Th17 cells in mouse spleen CD4 + T cells treated with an SCD1 inhibitor. Additionally, pri‐miR‐192‐5p expression was increased in CD4 + T cells isolated from the peripheral blood of asthmatic children, and the deletion of METTL3 upregulated pri‐miR‐192‐5p expression in an m6A‐dependent manner. MiR‐192‐5p mimic and inhibitor both reversed miR‐192‐5p and SCD1 expression affected by overexpression or deletion of METTL3, both in vivo and in vitro . Furthermore, METTL3 overexpression attenuated lung inflammation, el...