m6A修饰的长链非编码RNA AK155053通过miR-212-5p/Ptgs2轴调控铁死亡参与小鼠脑创伤的机理研究

创伤性脑损伤（TBI）的病死率和致残率极高，已成为神经系统疾病常见的危急重症。研究显示，TBI后出现一种新的死亡方式——铁死亡，并存在长链非编码RNA（lncRNA）的差异表达，但lncRNA是否通过铁死亡介导TBI发病尚不清晰。课题组前期发现一个全新的lncRNA AK155053在小鼠TBI后显著高表达，受m6A修饰，可调控铁死亡；并且miR-212-5p靶向Ptgs2抑制铁死亡发挥神经保护作用。生物信息学和双荧光素酶报告基因实验证实AK155053可结合miR-212-5p。由此推测，AK155053可能通过miR-212-5p/Ptgs2轴调控铁死亡参与TBI发病。本项目拟通过体内体外实验论证AK155053的生物学功能，采用RIP、MeRIP和转录组测序等方法解析其分子机理及m6A修饰状态，旨在阐明AK155053在小鼠TBI中的作用及其调控机制，为TBI的药物干预提供新靶点。

Traumatic brain injury (TBI) is a common critical illness in neurological diseases, with high mortality and disability rate. Previous studies have shown that a novel cell death (i.e., ferroptosis) was induced and a large number of long non-coding RNAs (lncRNAs) were differentially expressed following TBI. However, whether lncRNAs are involved in TBI via regulating ferroptosis is not fully elucidated. In our previous work, we found a novel lncRNA AK155053 using high-throughput sequencing. The m6A modified AK155053 was over-expressed in mice after TBI, with a function of regulating ferroptosis. Moreover, we found that miR-212-5p can inhibit ferroptosis and exert neuroprotective effect by targeting Ptgs2. Bioinformation analysis predicted that AK155053 may be used as a competitive endogenous RNA by binding to miR-212-5p, which was confirmed by dual luciferase reporter assay. Based on this background, we hypothesized that lncRNA AK155053 may participate in the ferroptosis of TBI through the regulation of miR-212-5p/Ptgs2 axis. In this study, we plan to demonstrate the biological function of AK155053 both in vitro and in vivo. The molecular mechanism and m6A modification of AK155053 will also be explored using a series of assays, such as RNA immunoprecipitation, methylated RNA immunoprecipitation and transcriptome sequencing. Our purpose was to elucidate the role of AK155053 in mice after TBI and its regulatory mechanism, and provide a new target for drug treatment of TBI.