LncRNA BDNF-AS as ceRNA regulates the miR-9-5p/BACE1 pathway affecting neurotoxicity in Alzheimer's disease
LncRNA BDNF-AS as ceRNA regulates the miR-9-5p/BACE1 pathway affecting neurotoxicity in Alzheimer's disease
复制标题
DOI：
10.1016/j.archger.2021.104614
复制
发表时间：
2022-01-03
影响因子：
4
通讯作者：
Cao, Yongjun
中科院分区：
文献类型：
--
作者：
Ding, Yuting;Luan, Wenkang;Cao, Yongjun
简介：脑源性营养因子反义RNA（Brain-derived nutritional factor antisense RNA，BDNF-AS）是一种反义RNA，已被证明在某些神经系统疾病的发生和发展中起着至关重要的作用。然而，BDNF-AS在阿尔茨海默病（AD）中的作用和分子机制尚未阐明yet.Methods：外周血样本收集AD门诊患者以及从正常老年人在社区，和BDNF-AS的表达进行了分析，采用定量逆转录-聚合酶链反应。建立体外模型，采用CCK 8法和流式细胞术检测BDNF-AS表达水平对细胞的影响。结果：AD患者外周血中BDNF-AS表达增高，且BDNF-AS表达增高可能与AD患者的认知功能状态有关。结果证实，在体外模型中，BDNF-AS可促进神经毒性。然后，我们发现BDNF-AS通过竞争性结合miR-9- 5 p促进BACE 1的表达，从而促进淀粉样蛋白沉积。最后，通过Morris水迷宫实验，我们发现BDNF-AS的高表达促进了AD小鼠的认知功能损害。结论：BDNF-AS在AD的发生发展中起着至关重要的作用。BDNF AS作为一个新的AD致病基因，有可能作为AD患者的治疗靶点或预后指标。
Introduction: The long non-coding RNA Brain-derived nutritional factor anti-sense RNA (BDNF-AS) is a type of anti-sense RNA that has been proven to play a crucial role in the occurrence and development of certain nervous system disorders. However, the role and molecular mechanism of BDNF-AS in Alzheimer's disease (AD) have not been elucidated yet.Methods: Peripheral blood samples were collected from outpatients with AD as well as from normal elderly individuals in the community, and the expression of BDNF-AS was analysed using quantitative reverse transcription-polymerase chain reaction. An in vitro model was constructed, and the effect of BDNF-AS expression level on the cells was measured using the CCK8 method and flow cytometry. The molecular biological mechanism of BDNF-AS in AD was examined using the luciferase reporter, MS2-RIP, and RNA pulldown assays.Result: We found that the expression of BDNF-AS was elevated in the peripheral blood of patients with AD and that increased BDNF-AS expression may be associated with the cognitive status of such patients. The results confirmed that BDNF-AS could promote neurotoxicity in the in vitro model. Then, we uncovered that BDNF-AS promotes the expression of BACE1 through the competitive binding of miR-9-5p, thereby promoting amyloid deposition. Finally, through the Morris water maze, we found that the high expression of BDNF-AS promoted cognitive impairment in AD mice.Conclusion: The obtained results suggest that BDNF-AS plays a crucial role in the occurrence and development of AD. As a new pathogenic gene of AD, BDNF-AS may be used as a therapeutic target or as a prognostic marker in patients with AD.