LncRNAPPIHP1-201通过NDUFAB1介导线粒体损伤在早发精神分裂症中的作用机制研究

早发精神分裂症（EOS）危害严重，病因未明，探明该病的表观遗传机制具有重要价值。本项目前期工作发现与该病相关的LncRNAPPIHP1-201，其与mRNANDUFAB1相关并参与线粒体损伤；预实验在人体以及细胞水平验证了二者之间的调控关系。结合线粒体功能障碍假说，我们提出：LncRNAPPIHP1-201通过抑制NDUFAB1表达引起线粒体损伤参与EOS发病。本项目拟开展以下研究：（1）从动物和人体层面阐明PPIHP1-201是否参与EOS发病；（2）利用PPIHP1-201和NDUFAB1过表达/沉默的动物模型探讨PPIHP1-201是否通过NDUFAB1引起线粒体损伤，明确PPIHP1-201发挥作用的机制；（3）从细胞层面分析PPIHP1-201与NDUFAB1二者的直接调控关系。本项目将有助于揭示lncRNA参与精神分裂症线粒体损伤的分子调控机制。

Early-onset schizophrenia (EOS) is a serious disease, while the cause of the disease is still unknown. It is important to explore the pathological mechanism of EOS. In our preliminary work, we found that lncRNAPPIHP1-201was related to EOS. We also found the lncRNA was related to mRNANDUFAB1 and involved in mitochondrial damage. In our pre-experiments, the correlation between the expression of PPIHP1-201 and NDUFAB1 were verified at the human and cellular level. Combined with the hypothesis of mitochondrion dysfunction in schizophrenia, we propose the hypothesis that “LncRNAPPIHP1-201 may cause mitochondrial damage via inhibition of NDUFAB1 and participate in the development of EOS”. Based on this, this project will carry out the following research : (1) To clarify whether PPIHP1-201 is involved in the pathogenesis of EOS from the animal and human level; (2) To explore whether PPIHP1-201 can cause mitochondrial damage via inhibition of NDUFAB1 by establishing animal models of PPIHP1-201 over-express/knock-out and NDUFAB1 over-express/knock-out, and to clarify the mechanism of PPIHP1-201; (3) Finally, to analyze the direct regulatory relationship between PPIHP1-201 and NDUFAB1 in cell experiments. This project will help reveal the molecular regulation mechanism of LncRNA involved in mitochondrial damage in schizophrenia.