BACE1- as通过调节BACE1 mRNA表达对β-淀粉样蛋白生成的影响

IF 2.946 Q3 Biochemistry, Genetics and Molecular Biology BMC Molecular Biology Pub Date : 2019-10-01 DOI:10.1186/s12867-019-0140-0

Fan Li, Yun Wang, Hui Yang, Yingying Xu, Xiaoyan Zhou, Xiao Zhang, Zhaohong Xie, Jianzhong Bi

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引用次数: 24

摘要

BACE1反义转录物(BACE1- as)是一种保守的长链非编码RNA (lncRNA)。AD组BACE1- as水平显著升高，BACE1 mRNA水平略有升高。BACE1- as对BACE1 mRNA的表达有明显的调节作用，促进了a β的形成。SH-SY5Y细胞和C57/BL6J小鼠给予Aβ1-42后，检测BACE1- as、BACE1 mRNA和BACE1蛋白的表达以及Aβ1-40的浓度。然后，我们使用靶向BACE1- as的sirna在SH-SY5Y和20E2细胞中沉默BACE1- as的表达，并检测其对BACE1 mRNA和BACE1蛋白水平以及Aβ1-40代的影响。Aβ1-42增加了SH-SY5Y细胞和C57BL/6J小鼠脑内BACE1- as、BACE1 mRNA和蛋白的表达以及Aβ1-40的浓度。BACE1- as siRNA预处理抑制了a - β1-42增加BACE1- as和BACE1表达以及a - β生成的作用。外源Aβ1-42诱导BACE1表达和产生的机制是由BACE1- as介导的。BACE1- as参与了APPsw转基因细胞中BACE1表达和Aβ生成的调控机制。

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The effect of BACE1-AS on β-amyloid generation by regulating BACE1 mRNA expression

The BACE1 antisense transcript (BACE1-AS) is a conserved long noncoding RNA (lncRNA). The level of BACE1-AS is significantly increased and the level of the BACE1 mRNA is slightly increased in subjects with AD. BACE1-AS exerts a significant moderating effect on the expression of the BACE1 mRNA and promotes the formation of Aβ. After the administration of Aβ_1-42 to SH-SY5Y cells and C57/BL6J mice, we detected the expression of BACE1-AS, BACE1 mRNA, and BACE1 protein, as well as the concentration of Aβ_1-40. Then, we silenced the expression of BACE1-AS in SH-SY5Y and 20E2 cells using siRNAs targeting BACE1-AS and detected its effects on the levels of the BACE1 mRNA and BACE1 protein and Aβ_1-40 generation.

The administration of Aβ_1-42 increased the expression of BACE1-AS, BACE1 mRNA and protein, as well as the concentration of Aβ_1-40 in SH-SY5Y cells and the brains of C57BL/6J mice. Pretreatment with the BACE1-AS siRNA inhibited the effect of Aβ_1-42 on increasing the expression of BACE1-AS and BACE1, as well as the generation of Aβ.

The mechanism by which exogenous Aβ_1-42 induces BACE1 expression and Aβ generation is mediated by BACE1-AS. BACE1-AS is involved in the mechanism regulating BACE1 expression and Aβ generation in APPsw transgenic cells.

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来源期刊

BMC Molecular Biology 生物-生化与分子生物学

CiteScore

4.80

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： BMC Molecular Biology is an open access journal publishing original peer-reviewed research articles in all aspects of DNA and RNA in a cellular context, encompassing investigations of chromatin, replication, recombination, mutation, repair, transcription, translation and RNA processing and function.