Circ_0059256/miR-130b-3p/TBP2轴调控HLECs响应氧化应激的机制研究

本课题组曾首次报道硫氧还蛋白结合蛋白2（TBP2）介导H2O2浓度依赖性的细胞自噬、细胞凋亡，并发现低浓度H2O2处理人晶状体上皮细胞（HLECs）诱导TBP2表达增加，且TBP2的mRNA水平上调，靶向TBP2的miR-130b-3p下调，吸附miR-130b-3p的Circ_0059256上调。为深入研究，本项目拟采用CRISPR/Cas9基因编辑技术、Northern、CLIP等技术分析Circ_0059256/miR-130b-3p/TBP2轴调控HLECs响应氧化应激的机制，并探索Circ_0059256来源FASTKD5基因的转录因子对该轴的调控。项目预期系统阐明氧化应激条件下Circ_0059256/miR-130b-3p/TBP2轴之间的相互调控，揭示HLECs进行自我防御和保护的分子机制，为今后研制有效的靶向防治提供理论依据，可望有效抑制和延缓年龄相关性白内障的发病。

Thioredoxin binding protein 2 (TBP2) regulates apoptosis and autophagy which are dependent on concentrations of H2O2, and its expression increases after low concentration of H2O2 treatment. With the up-regulation of TBP2 mRNA level, miR-130b-3p targeting TBP2 was down-regulated, and Circ_0059256 sponging miR-130b-3p was up-regulated. To elucidate the role of the Circ_0059256/ miR-130b-3p/TBP2 axis under oxidative stress and its underlying mechanism, with helps of CRISPR/Cas9 gene editing technology, Northern blot, CLIP and so on, this.project will investigate the effect of the Circ_0059256/ miR-130b-3p/TBP2 axis in cellular oxidative stress, also identify the regulation of FASTKD5, which can generate Circ_0059256, in the Circ_0059256/ miR-130b-3p/TBP2 axis. This study will describe the mutual regulation between the Circ_0059256/ miR-130b-3p/TBP2 axis under oxidative stress, cast light on the molecular mechanisms of HLECs' response to oxidative stress. These expected findings will provide new therapeutic strategies for cataract by targeting oxidative stress, and will be beneficial to the aging population and communities.