Gong Guohua, An Fengmao, Wang Yu, Bian Ming, Yu Li-Jun, Wei Chengxi
Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for The Nationalities, Tongliao, Inner Mongolia, P.R. China.
Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, P.R. China.
Oncotarget. 2017 Sep 21;8(53):91551-91557. doi: 10.18632/oncotarget.21177. eCollection 2017 Oct 31.
Beta-site Amyloid precursor protein Cleaving Enzyme 1 (BACE1) is conceived as a potential target for therapies against Alzheimer disease (AD). MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression in a sequence-specific manner. Although miRNAs have been increasingly recognized as important modulators in sporadic AD. In order to confirm whether miR-15b correlates with the BACE1 upregulation in sporadic AD, we firstly evaluated the expression of miR-15b and BACE1 in sporadic AD brain tissues and analyzed the correlation of miR-15b with BACE1. Then we determined the regulation of miR-15b in SH-SY5Y cells on the BACE1 expression. And finally we determined the targeting to 3' UTR of BACE1 by miR-15b by a luciferase reporter. Downregulation of miR-15b alleviated Aβ-induced viability inhibition and decreased apoptosis in SH-SY5Y cells. Our results demonstrated that miR-15b play an important role in the cellular AD phenotype and might be involved in the pathogenesis of AD.
β-位点淀粉样前体蛋白裂解酶1（BACE1）被认为是治疗阿尔茨海默病（AD）的潜在靶点。微小RNA（miRNA）是一类小的非编码RNA，它们以序列特异性方式负调控基因表达。尽管miRNA已越来越被认为是散发性AD中的重要调节因子。为了证实miR-15b是否与散发性AD中BACE1的上调相关，我们首先评估了散发性AD脑组织中miR-15b和BACE1的表达，并分析了miR-15b与BACE1的相关性。然后我们确定了miR-15b在SH-SY5Y细胞中对BACE1表达的调控作用。最后，我们通过荧光素酶报告基因确定了miR-15b对BACE1 3'UTR的靶向作用。miR-15b的下调减轻了Aβ诱导的SH-SY5Y细胞活力抑制并减少了细胞凋亡。我们的结果表明，miR-15b在细胞AD表型中起重要作用，可能参与了AD的发病机制。
