LncRNA-HOXA-AS2经EZH2/miR34a调节mtTFA甲基化在 COPD肺血管内皮细胞凋亡中的作用

我们既往研究发现miR34a通过调节mtTFA甲基化所致的肺血管内皮细胞凋亡在COPD发病中具有重要意义。但miR34a上游调控机制尚不清楚。我们近期研究发现lncRNA-HOXA-AS2在COPD患者肺组织中显著下调并与肺血管内皮细胞凋亡相关。通过生物信息学软件及文献检索发现HOXA-AS2可与EZH2结合，而EZH2可表观调控miR34a的表达且需lncRNA的介导。因而我们推测COPD中HOXA-AS2可能通过与EZH2结合调控miR34a，进而调节mtTFA甲基化。本研究从人体、动物试验和体外细胞实验入手，探讨在COPD中HOXA-AS2能否结合EZH2表观调控miR34a进而调节mtTFA甲基化，参与COPD的发病。

In our previous research, over expression of miR34a, which contributed to pulmonary vascular endothelial cells(PVECs) apoptosis via promoting methylation of mtTFA has played a significant role in the pathogenesis of COPD. However, the upstream regulatory mechanism of miR34a remains unclear in COPD. We have recently found that the level of HOXA-AS2 was obviously decreased in the lung tissue of subjects with COPD and was closely related to PVEC apoptosis. The bioinformatics software demonstrated that HOXA-AS2 could be coupled with EZH2, moreover, EZH2 has been proved to epigenetically regulate miR34a by the mediation of lncRNA. Therefore, we speculate that the complex of HOXA-AS2 and EZH2 may regulate the expression of miR34a which then control the methylation of mtTFA in COPD. In this study, we plan to demonstrate whether HOXA-AS2 can epigenetically regulate miR34a through being coupled with EZH2 to mediate the methylation of mtTFA in COPD.