circRNA-19038与lncRNA-AK016022共调控Vegfa在早产脑损伤中的作用和机制研究

lncRNA-AK016022是我们采用芯片技术在早产炎症脑损伤动物脑组织首次筛选到的一条高度保守、高差异表达的lncRNA，并在细胞水平证实其下调mRNA-Vegfa参与早产脑白质损伤；进一步研究差异基因发现circRNA-19038亦调控mRNA-Vegfa表达。提示circRNA与lncRNA在Vegfa调控通路中有交互作用。基于cirRNA通过与lncRNA等生物分子多层次调控基因，具时间特异性、结构更稳定，在脑和血液更高的检测灵敏度、体外调控可行。本研究拟利用FISH、基因敲除和过表达技术，探明circRNA-19038在脑组织内的定位定量，寻找与lncRNA-AK016022的时空关系及交互调控机制；利用靶向调控、行为学实验，探究体外调控circRNA-19038的可能、效果和安全性。研究具源头创新性，将为揭示早产儿脑发育和损伤机制及防治提供的新的理论和干预靶标。

LncRNA-AK016022 is a highly conserved and differentially expressed lncRNA that we first screened from the brain tissues of premature animals with inflammatory brain injury by lncRNA microarray，and its down-regulation of mRNA-vegfa was confirmed to be involved in preterm brain white matter injury at the cellular level.We also find circRNA-19038 regulated mRNA-Vegfa expression.It is suggested that circRNA interacts with lncRNA in Vegfa regulatory pathway.Based on cirRNA, the multi-layer regulatory genes with lncRNA and other biomolecules are more time-specific and structurally stable, with higher detection sensitivity in brain and blood ,and feasible in vitro regulation.In this study, FISH, gene knockout and overexpression techniques will be used to investigate the location and quantification of circRNA-19038 in brain tissues, and to find the spatio-temporal relationship with lncRNA-AK016022 and its interactive regulatory mechanism.The possibility, effect and safety of regulation of circrna-19038 in vitro will be investigated by targeted regulation and behavioral experiments.The research is original and innovative, and will provide new theories and intervention targets for revealing the mechanism of brain development , injury ,prevention and treatment of premature infants.