LINC00152经miR-16-5p调控Wip1/NF-κB负反馈环影响视网膜星形胶质细胞炎性活化的分子机制

星形胶质细胞介导的神经炎症在视网膜退行性疾病中发挥关键作用。课题组已证实，Wip1/NF-κB负反馈环是维持星形胶质细胞活化平衡的关键，但其调控网络尚不清楚。预实验显示，非编码RNA miR-16-5p存在调控Wip1的位点，且LINC00152具备调控miR-16-5p的潜能。因此，我们提出假说：LINC00152经miR-16-5p调控Wip1/NF-κB负反馈环，进而影响星形胶质细胞介导的神经炎症。我们拟首先确认miR-16-5p能特异结合Wip1，并影响其表达和下游功能；通过lncRNA芯片测序和序列分析，筛选出LINC00152是参与miR-16-5p调控的关键lncRNA；从分子、细胞及大体水平，分层干预并阐明LINC00152影响miR-16-5p的分子机制，及其对Wip1/NF-κB负反馈环、星形胶质细胞炎性活化和视功能的影响。研究成果将为神经炎症相关眼病提供新的治疗靶点。

Astrocyte-mediated neuroinflammation plays a key role in retinal degenerative diseases. Our team has confirmed that Wip1/NF-κB negative feedback loop is the key to maintain the balance of inflammatory activation of astrocytes, but its regulatory network is still unclear. Our Pre-experiments showed that there were miR-16-5p binding site on Wip1 coding gene, and LINC00152 had the potential to regulate miR-16-5p. Therefore, we hypothesize that LINC00152 regulates the negative feedback loop of Wip1/NF-κB via miR-16-5p, thereby affecting retinal astrocyte-mediated neuroinflammation. We intend to confirm that miR-16-5p can specifically bind to Wip1 and affect its expression and downstream function. Through lncRNA microarray and sequence analysis, LINC00152 is selected as the key lncRNA involved in the regulation of miR-16-5p. The molecular mechanism of LINC00152 affecting miR-16-5p and its negative feedback loop to Wip1/NF-κB and astrocytic inflammation are elucidated in the molecular, cellular and general levels. The research results will provide a new therapeutic target for neuroinflammation-related ophthalmopathy.