YTHDC1 mitigates ischemic stroke by promoting Akt phosphorylation through destabilizing PTEN mRNA
Zhaolong Zhang, Qiuhan Wang, Xiaolong Zhao, Liming Shao, Guoping Liu, Xuan Zheng, Lingling Xie, Yan Zhang, Chengjian Sun, Rui Xu
Abstract
Abstract YTH Domain Containing 1 (YTHDC1) is one of the m 6 A readers that is essential for oocyte development and tumor progression. The role of YTHDC1 in neuronal survival and ischemic stroke is unknown. Here, we found that YTHDC1 was unregulated in the early phase of ischemic stroke. Knockdown of YTHDC1 exacerbated ischemic brain injury and overexpression of YTHDC1 protected rats against brain injury. Mechanistically, YTHDC1 promoted PTEN mRNA degradation to increase Akt phosphorylation, thus facilitating neuronal survival in particular after ischemia. These data identify YTHDC1 as a novel regulator of neuronal survival and modulating m 6 A reader YTHDC1 may provide a potential therapeutic target for ischemic stroke.