HuR介导炎症因子促进翼状胬肉发展的表观遗传调控机制

Inflammation is one of the important causes for pterygium progression and recurrence. Post-transcriptional regulation by RNA binding protein HuR and their interaction with microRNAs, is a form of epigenetic regulation that is closely associated with many diseases. We have previously found that miR-122 was involved in the regulation of pterygium epithelial cells apoptosis, HuR expression was elevated in pterygium and IL-1β induced nuclear to cytoplasm transfer of HuR in pterygium cells. Moreover, bioinformatic analysis showed HuR could bind to the mRNA of IL-1β and MMP-9. We suppose that HuR is critical in the process of inflammation induced pterygium progression. We plan to change the expression level of HuR, investigate the role of HuR in the signaling pathway of inflammatory factors, cell proliferation, apoptosis, migration, fibrosis and angiogenesis. We will also determine the combination of HuR to target mRNA and subsequent post-transcriptional regulation as well as the potential interaction with microRNAs with RNA-IP, biotin pull-down and M2 system RNA location technique, and analyze the association between HuR expression in pterygium tissue with histopathology and clinical manifestation. This project aims to obtain deep insight into the molecular mechanism of pterygium progression and recurrence and explore the potentially effective intervention, thus is of great importance for clinical practice.

炎症是促进翼状胬肉进展和复发的重要原因。RNA结合蛋白HuR与某些mRNA结合发挥的转录后调控以及与microRNA之间相互作用的表观遗传调控机制与很多疾病有密切关系。我们前期研究发现miR-122参与调控胬肉上皮细胞的凋亡，胬肉组织中HuR表达增加，IL-1β可以诱导胬肉细胞中HuR发生胞核-胞浆转移，生物信息学分析表明HuR可以结合IL-1β和及MMP9的mRNA。我们推测HuR是介导炎症因子促进翼状胬肉进展的重要分子，拟通过基因水平调节HuR表达，检测HuR对炎症因子信号传导、增殖、凋亡、迁移、纤维化及血管新生的影响，通过RNA-IP、biotin pull-down等检测HuR与靶基因mRNA结合及转录后调控及与microRNA的相互作用，在临床样本检测HuR表达与组织病理学和临床表现之间关系。本课题深入研究翼状胬肉进展和复发的分子机制和探索可能的治疗手段，具有重要临床意义。

炎症是促进翼状胬肉进展和复发的重要原因。RNA结合蛋白HuR与某些mRNA结合发挥的转录后调控以及与microRNA之间相互作用的表观遗传调控机制与很多疾病有密切关系。我们前期研究发现miR-122参与调控胬肉上皮细胞的凋亡，胬肉组织中HuR表达增加，IL-1β可以诱导胬肉细胞中HuR发生胞核-胞浆转移，生物信息学分析表明HuR可以结合IL-1β和及MMP9的mRNA。我们推测HuR是介导炎症因子促进翼状胬肉进展的重要分子，拟通过基因水平调节HuR表达，检测HuR对炎症因子信号传导、增殖、凋亡、迁移、纤维化及血管新生的影响，通过RNA-IP、biotin pull-down等检测HuR与靶基因mRNA结合及转录后调控及与microRNA的相互作用，在临床样本检测HuR表达与组织病理学和临床表现之间关系。本课题深入研究翼状胬肉进展和复发的分子机制和探索可能的治疗手段，具有重要临床意义。