LncRNA B230334C09Rik通过miR-543-3p靶向调节GLT-1参与帕金森病发病的机制研究

LncRNA、miRNA在疾病发生中的调控效应越来越受到重视，但是目前PD中对非编码RNA的调控分子机制研究还相对匮乏。我们前期研究发现PD小鼠miR-543-3p表达增高，并下调了靶分子GLT-1表达，鉴定了miR-543-3p的海绵分子lncRNA B230334C09Rik，抑制miR-543-3p可以显著改善PD小鼠的病理学异常。据此推测：PD发病中lncRNA B230334C09Rik--miR-543-3p--GLT-1轴的异常发挥了一定的致病效应，加重了谷氨酸兴奋性神经毒性效应，促进了神经元退行性变化。本项目将鉴定PD发病中重要lncRNA、miRNA，从分子水平、细胞水平、整体水平揭示LncRNA B230334C09Rik、miR-543-3p在PD发病中的作用与机制，探讨miR-543-3p作为治疗靶标及早期诊断标志物的可能性。本项目将为PD防治和药物研发提供新线索。

The regulatory effect of lncRNA and miRNA in the occurrence of diseases has been increasingly valued, however, the research on the regulatory molecular mechanism of non-coding RNA in PD is still relatively scarce. Our previous study found that the expression of miR-543-3p was increased, and miR-543-3p down-regulates the expression of target molecule GLT-1 in PD mice. We also identify the sponge molecule of miR-543-3p, lncRNA B230334C09Rik. We found that inhibition of miR-543-3p can significantly improve pathological abnormalities in PD mice. So we hypothesize that the abnormality of lncRNA B230334C09Rik--miR-543-3p--GLT-1 axis plays a certain pathogenic effect in the pathogenesis of PD, which aggravates the neurotoxic effect of glutamate and promotes neuronal degeneration. In this project we will identify the important lncRNA, miRNA in the pathogenesis of PD, reveal the roles and mechanisms of LncRNA B230334C09Rik and miR-543-3p in the pathogenesis of PD from the molecular level, cellular level and overall level. We will explore the potential of miR-543-3p as therapeutic targets and early diagnostic markers. This study will provide a new approach for the treatment, prevention and drug development of PD.