“分子诱饵”LncRNA H19通过海绵吸附miR-19a/b调控Id2在脑缺血中的作用及机制

Further investigating the pathophysiological mechanism of ischemia/hypoxia induced neuronal injury and enhancing the therapeutic effect are always of great importance and difficulty for neuroscience researchers. In the previous work we found Id2 can promote the neuronal apoptosis induced by ischemia/hypoxia; but the absence of Id2 targeted inhibitor limited its application. Thus, seek the upstream regulating factor of Id2 (non-coding RNAs, for example) is of great importance. Bioinformatics prediction found LncRNA H19, miR-19 a/b are the upstream regulating factors of Id2. Furthermore, preliminary experiments found that the expressions of LncRNA H19 and Id2 were up-regulated in neuronal cells after the exposure of ischemia/hypoxia, while the expression of miR-19a/b was down-regulated; LncRNA H19 might regulate Id2 expression via miR-19a/b. Based on the above research and the regulation mechanisms of non-coding RNAs, we hypothesize that: LncRNA H19 might regulate Id2 expression via miR-19a/b by functioning as miRNA sponges in the brain ischemia. In this research, with the aid of the function experiments, RNA immunecoprecipitation and luciferase reporter gene experiment, we aim to verify the funcition and mechanims of LncRNA H19 modulating Id2, and at last to provide basis for the basic research and clinical treatment of cerebral ischemia.

深入探讨脑缺血损伤的病理生理机制，提高治疗效果一直是神经科学研究的难点和重点。前期研究发现Id2促进了缺血/缺氧诱导的神经凋亡，但Id2靶向抑制剂的缺乏限制了其应用前景；正因此，研究调控Id2的上游因子（如非编码RNAs）显得尤为重要。生物信息学预测发现LncRNA H19、miR-19a/b可能是调控Id2的上游因子。预实验发现：在缺血/缺氧的神经细胞中，Id2和LncRNA H19表达上调，而miR-19a/b表达下调；同时还发现，miR-19a/b介导了LncRNA H19调控Id2的表达。基于上述结果和非编码RNAs的调控机制，我们推测：在缺血/缺氧性神经损伤中，LncRNA H19通过“海绵吸附”miR-19a/b调控Id2的表达。本研究拟通过功能实验、RNA免疫共沉淀和荧光素酶报告基因实验验证LncRNA H19调控Id2的作用及分子机制，为脑缺血的基础研究和临床治疗提供依据。

深入探讨脑缺血损伤的病理生理机制，提高治疗效果一直是神经科学研究的难点和重点。前期研究发现Id2促进了缺血/缺氧诱导的神经凋亡，进一步研究发现LncRNA H19、miR-19a/b可能是调控Id2的上游因子。本研究发现：在缺血/缺氧的神经细胞中，Id2和LncRNA H19表达上调，而miR-19a/b表达下调；同时还发现，miR-19a/b介导了LncRNA H19调控Id2的表达。基于上述研究发现和非编码RNAs的调控机制，我们进一步通过功能实验、RNA 免疫共沉淀和荧光素酶报告基因实验证实了在缺血/缺氧性神经损伤中，LncRNA H19通过“海绵吸附”miR-19a/b调控Id2的表达。本研究成果可为脑缺血的基础研究和临床治疗提供依据。